Raltegravir (MK-0518)

For research use only. Not for use in humans.

目录号：S2005 中文名称：拉替拉韦，雷特格韦

Raltegravir (MK-0518) Chemical Structure

CAS No. 518048-05-0

Raltegravir (MK-0518)是一种有效的integrase (IN)抑制剂，作用于WT和S217Q PFV IN，在无细胞试验中IC50分别为90 nM和40 nM。它对HIV-1 IN的选择性比对其他相关Mg2+依赖性酶要高1000倍以上，如HCV聚合酶、HIV反转录酶、HIV RNaseH、人类α-, β-, γ-聚合酶。

规格

价格

库存

购买数量

10mM (1mL in DMSO)	RMB 1722.95	现货
5mg	RMB 983.46	现货
10mg	RMB 1729.52	现货
50mg	RMB 5494.35	现货
200mg	RMB 10401.3	现货
大包装	有超大折扣

大剂量询单有大折扣!

今日订购，明日送达，全国免运费！

全国免费电话：400-668-6834 | Email：info@selleck.cn

客户使用Selleck生产的Raltegravir (MK-0518)发表文献46篇：

Cancer Cell, 2019, 36(4):385-401

PubMed: 31564637 ( click the link to review the publication )

Nature, 2016, 530(7590):358-61

PubMed: 26887496 ( click the link to review the publication )

Proc Natl Acad Sci U S A, 2021, 118(10)e2005568118

PubMed: 33649200 ( click the link to review the publication )

Int J Nanomedicine, 2021, 16:1189-1206

PubMed: 33623382 ( click the link to review the publication )

EBioMedicine, 2021, 65:103241

PubMed: 33647768 ( click the link to review the publication )

J Immunol, 2020, 204(5):1242-1254

PubMed: 31988180 ( click the link to review the publication )

J Virol, 2020, JVI.01386-20

PubMed: 33298546 ( click the link to review the publication )

J Virol, 2020, JVI.01247-20

PubMed: 33239456 ( click the link to review the publication )

Blood Adv, 2020, 12;4(9):1845-1858

PubMed: 32369565 ( click the link to review the publication )

AIDS, 2019, 33(2):199-209

PubMed: 30562171 ( click the link to review the publication )

J Virol, 2019, 93(9)

PubMed: 30760577 ( click the link to review the publication )

JCI Insight, 2019, 4(12)

PubMed: 31217351 ( click the link to review the publication )

Nat Commun, 2018, 9(1):3450

PubMed: 30150664 ( click the link to review the publication )

Elife, 2018, 7e36245

PubMed: 29941091 ( click the link to review the publication )

Mol Ther, 2018, 26(6):1435-1446

PubMed: 29724686 ( click the link to review the publication )

mBio, 2018, 9(6)

PubMed: 30401776 ( click the link to review the publication )

PLoS Pathog, 2018,

PubMed: 29470552 ( click the link to review the publication )

J Infect Dis, 2018, 218(11):1773-1776

PubMed: 30010985 ( click the link to review the publication )

J Virol, 2018, 92(6)

PubMed: 29298886 ( click the link to review the publication )

Virol J, 2018, 15(1):152

PubMed: 30285810 ( click the link to review the publication )

JCI Insight, 2018, 3(19)

PubMed: 30282829 ( click the link to review the publication )

Cell Host Microbe, 2018, 24(3):392-404

PubMed: 30173955 ( click the link to review the publication )

J Clin Invest, 2017, 127(12):4352-4364

PubMed: 29083319 ( click the link to review the publication )

Cell Rep, 2017, 18(5):1324-1334

PubMed: 28147284 ( click the link to review the publication )
Cell Death Dis, 2017, 8(6):e2852

PubMed: 28569776 ( click the link to review the publication )

J Virol, 2017, 91(24)

PubMed: 29021396 ( click the link to review the publication )

Antimicrob Agents Chemother, 2017, 61(8)

PubMed: 28533248 ( click the link to review the publication )

Wellcome Open Res, 2017, 2:87

PubMed: 29062917 ( click the link to review the publication )

Nucleic Acids Res, 2016, 44(14):6896-906

PubMed: 27369381 ( click the link to review the publication )

Front Microbiol, 2016, 7:1944

PubMed: 27990142 ( click the link to review the publication )

Bioorg Med Chem, 2016, 24(11):2410-22

PubMed: 27117260 ( click the link to review the publication )

Sci Signal, 2015, 8(399):ra104

PubMed: 26486173 ( click the link to review the publication )

Antimicrob Agents Chemother, 2015, 10.1128/AAC.00114-15

PubMed: 25779572 ( click the link to review the publication )

Virology, 2015, 484:364-76

PubMed: 26186575 ( click the link to review the publication )

Antimicrob Agents Chemother, 2014, 58(6):3168-76

PubMed: 24663015 ( click the link to review the publication )

Antimicrob Agents Chemother., 2014, 58(8):4431-42

PubMed: 24867983 ( click the link to review the publication )

PLoS One, 2014, 9(8):e105617

PubMed: 25144636 ( click the link to review the publication )

PLoS Pathog, 2013, 9(1):e1003125

PubMed: 23349632 ( click the link to review the publication )

J Virol, 2013, 87(17):9768-79

PubMed: 23824795 ( click the link to review the publication )

Retrovirology, 2013, 10:144

PubMed: 24261564 ( click the link to review the publication )

PLoS One, 2013, 8(11):e81489

PubMed: 24282600 ( click the link to review the publication )

Sci Rep, 2013, 3:2103

PubMed: 23812503 ( click the link to review the publication )

Blood, 2012, 120(17):3488-90

PubMed: 22955925 ( click the link to review the publication )

J Virol, 2012, 86(17):9337-50

PubMed: 22718820 ( click the link to review the publication )

Virus Res, 2012, 171(1):121-8

PubMed: 23201205 ( click the link to review the publication )

Vet Microbiol, 2011, 152(1-2):165-8

PubMed: 21570781 ( click the link to review the publication )

产品安全说明书

Integrase抑制剂选择性比较

生物活性

产品描述

特性

Raltegravir 是第一个被批准的人类免疫缺陷病毒1型（HIV-1）整合酶抑制剂。

靶点

Integrase (S217Q PFV) ^[1] (Cell-free assay)	Integrase (WT PFV) ^[1] (Cell-free assay)
40 nM	90 nM

体外研究

PFV整合携带S217H替换的IN，之后对 Raltegravir 的敏感性降低10倍，IC50为900 nM。PFV IN 具有10% WT 活性，且被Raltegravir抑制，IC50为200 nM,说明与 WT IN相比，对整合酶（IN）链转移抑制剂(INSTI)的敏感性降低约2倍。S217Q PFV IN 对 Raltegravir的敏感性至少与WT 酶相似。^[1] Raltegravir由葡萄糖醛酸化，而不是肝脏代谢而来。Raltegravir 在体外作用于人类T 淋巴细胞培养物，有效作用于HIV-1，抑制达95%时浓度为31±20 nM。Raltegravir作用于 CEMx174细胞，也有效作用于HIV-2,IC95为6 nM。Raltegravir 代谢主要通过葡萄糖醛酸化。葡萄糖醛酸化酶的强诱导剂UGT1A1显著降低 Raltegravir 浓度。Raltegravir 微弱抑制肝细胞色素 P450。Raltegravir不会诱导 CYP3A4 RNA 表达或 CYP3A4依赖的睾丸激素 6-β-羟化酶活性。^[2]在镁和钙存在时，Raltegravir细胞扩散性降低。^[3]Raltegravir 和相关的HIV-1整合酶 (IN) 链转移抑制剂 (INSTIs) 高效阻断病毒复制。^[4] Raltegravir 作用于急性感染人类淋巴 CD4⁺ T细胞系MT-4和 CEMx174, 高效抑制SIVmac251复制，EC90处于低纳摩尔范围。^[5]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
MT4	MlTYRY51cX[rcnHsJIF{e2G7			MUjBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDIeY1idiCrbX31co9l\W[rY3nlcoN6KH[rcoXzJFEhO0JiaX7m[YN1\WRiaX6gbJVu[W5iTWS0JINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZidnnyZYwhemWybHnjZZRqd25uIFXDOVAhRSByLkCwNVQh\|ryPLh?=	NFrvWpU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEW0NVczPid-MUi1OFE4OjZ:L3G+
MT-4	MnvpRY51cX[rcnHsJIF{e2G7			NGHFb21CdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJfW2jbjDpcY12dm:mZX\pZ4lmdmO7II\pdpV{KDFiM1KgbY5n\WO2ZXSgbY4hcHWvYX6gUXQuPCClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJJZqemGuIILldIxq[2G2aX;uMEBGSzVyIE2gNE4xODF6IN88UU4>	MlXUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThzNkC1NlEoRjF6MU[wOVIyRC:jPh?=
MT-4	M2W5XmFvfGm4aYLhcEBie3OjeR?=			M3zOTWFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JJZme2mldXzhdkB{fG:vYYTpeIl{KH[rcoXzJGcueHOndXTveJlx\WRiSIXtZY4hcW2vdX7v[IVncWOrZX7jfUB3cXK3czDpcoZm[3SnZDDpckBpfW2jbjDNWE01KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[geolz[WxicnXwcIlk[XSrb36sJGVEPTBiPTCwMlAxOiEQvF2u	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDF4MEWyNUc,OThzNkC1NlE9N2F-
MT2	MnvFRY51cX[rcnHsJIF{e2G7		NXTzS3d6OyC2bzC0JIRigXN?	MmjsRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSCQTEStN{Bqdm[nY4Tl[EBqdiCqdX3hckBOXDJiY3XscJMhdWWjc4Xy[YQh[W[2ZYKgN{B1dyB2IHThfZMh[nlibIXjbYZmemG\|ZTDy[ZBwenSncjDn[Y5mKGG\|c3H5MEBGSzVyIE2gNE4xODJizszNMi=>	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{OjB6MUCxNEc,OzJyOEGwNVA9N2F-
MT-2	M1\1bWFvfGm4aYLhcEBie3OjeR?=			MV7BcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKDOEIHnu[oVkfGWmIHnuJIh2dWGwIF3UMVIh[2WubIOgZpkhfHexIH\vcIQh\GmudYTpc44hdWW2aH;kJIlvKHC{ZYPlcoNmKG:oIEGwKUBHSlNuIFXDOVAhRSByLkCwN{DPxE1w	NFS1T4U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUGwOFAyOCd-MUmxNFQxOTB:L3G+
MT2	M3H3dmFvfGm4aYLhcEBie3OjeR?=		MYG1JIRigXN?	NXjHdml3SW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYMTCzRkBqdm[nY4Tl[EBqdiCqdX3hckBOXDJiY3XscJMh[W[2ZYKgOUBl[Xm\|IHL5JINp\W2rbIXtbY5me2OnbnPlJIlvKHC{ZYPlcoNmKG:oIH\leIFtKGKxdnnu[UB{\XK3bTygSWM2OCB;IECuNFA1KM7:TT6=	NIj0NHY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUK4OVM5QSd-MUmyPFU{QDl:L3G+
HOS	MXnBcpRqfmm{YXygZZN{[Xl?			MVLBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKGijcnLvdolv\yC5aXzkMZR6eGViaX70[Ydz[XOnIHnu[oVkfGWmIHnuJIh2dWGwIFjPV{Bk\WyuczygSWM2OCB;IECuNFA1KM7:TT6=	MmnmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF2OUOwOlYoRjJzNEmzNFY3RC:jPh?=
HOS	NUHVNVg3SW62aY\pdoFtKGG\|c3H5		MkXXN{BpenN?	MV\BcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDD3bYxlNXS7cHWgTJVu[W5iaX3teY5w\GWoaXPp[Y5kgSC4aYL1d{AyKGmwZnXjeIVlKGmwIFjPV{Bk\WyuczDwdoVqdmO3YnH0[YQh\m:{IEOgbJJ{KG[xbHzve4VlKGK7II\pdoFtKGmwZnXjeIlwdiCvZXHzeZJm\CCjZoTldkA1QCCqcoOgZpkhdHWlaX\ldoF{\SC{ZYDvdpRmeiCpZX7lJIF{e2G7LDDFR\|UxKD1iMD6wNFQh\|ryPLh?=	M4m0S\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NEexPFE3Lz5{NES3NVgyPjxxYU6=
MT2	NU\1dFZqSW62aY\pdoFtKGG\|c3H5		MlT1OUBl[Xm\|	NG\SfYdCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIEPCJIlvKE2WMjDj[YxteyCjZoTldkA2KGSjeYOsJGVEPTBiPTCwMlAxPiEQvF2u	NIrndYE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEKwO\|M6QCd-MUiyNFc{QTh:L3G+
MT-4	NE\nV3hCdnSrdnnyZYwh[XO\|YYm=			MnfERY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXKDFiUlnOJIhiemKxcnnu[{BqdnSnZ4Lhd4Uh\2WwZTDpcoZm[3SnZDDpckBOXC12IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4Yhfmm{dYOtbY5lfWOnZDDjfZRweGG2aHnjJIVn\mWldDDifUBOXFRiYYPzZZktKEWFNUCgQUAxNjByNjFOwG0v	MkHNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh\|N{i3NVMoRjF6M{e4O\|E{RC:jPh?=
MT4	MojDRY51cX[rcnHsJIF{e2G7			MXjBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKDOEIHnu[oVkfGWmIHnuJIh2dWGwIF3UOEBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oII\pdpV{NWmwZIXj[YQh[3m2b4DheIhq[yCnZn\lZ5Qh[nliTWTUJIF{e2G7LDDFR\|UxKD1iMD6wNFYh\|ryPLh?=	Mn;DQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MEC3NVgoRjJ2OUCwO\|E5RC:jPh?=
MT4	MojlRY51cX[rcnHsJIF{e2G7			NXn5Vot2SW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYLUGgN2IhcW6oZXP0[YQhcW5iaIXtZY4hVVR2IHPlcIx{KGG\|c3Xzd4VlKGG\|IIDyc5Rm[3Srb36gZYdicW6\|dDD2bZJ2ey2rbnT1Z4VlKGO7dH;wZZRpcWNiZX\m[YN1KGK7IF3UWEBie3OjeTygSWM2OCB;IECuNFA3KM7:TT6=	NU[4b3NERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3PVM{PjBpPkK0O\|k{OzZyPD;hQi=>
MT4	M3;qNGFvfGm4aYLhcEBie3OjeR?=			NETsdIpCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJfW2jbjDpcY12dm:mZX\pZ4lmdmO7II\pdpV{KDFiM1KgbY5n\WO2ZXSgbY4hcHWvYX6gUXQ1KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[geolzfXNiaX7keYNm\CCleYTvdIF1cGmlIHXm[oVkfCxiRVO1NEA:KDBwMEC2NUDPxE1w	Mkf4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB2N{myNFYoRjJyNEe5NlA3RC:jPh?=
MT4	MVvGeY5kfGmxbjDhd5NigQ>?		Mn;FNUBpeg>?	MofnTY5pcWKrdHnvckBw\iC5aXzkJJR6eGViSFnWNUA{SiCrbn\lZ5Rm\CCrbjDoeY1idiCPVESgZ4VtdHNidYPpcoch[2WubIOgdJJmNWmwY4XiZZRm\CC5aYToJINwdXCxdX7kJIZweiBzIHjyJI1m[XO3cnXkJFQh\GG7czDwc5N1KH[rcnHsJIlv\mWldHnvckBjgSCPVGSgZZN{[XluIFnDOVAhRSByLkCwOlIh\|ryPLh?=	MmDJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ7NkOxN\|UoRjJ{OU[zNVM2RC:jPh?=
MT4	NHPyVotCdnSrdnnyZYwh[XO\|YYm=			MWXBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKDOEIHnu[oVkfGWmIHnuJIh2dWGwIF3UOEBk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hd2ZidnnyeZMucW6mdXPl[EBkgXSxcHH0bI9o\W6rY3n0fUBjgSCPVGSgZZN{[XluIFXDOVAhRSByLkCwOlQh\|ryPLh?=	NGPVbVQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUS0O\|YzOSd-MUm0OFc3OjF:L3G+
MT-4	M3n0O2FvfGm4aYLhcEBie3OjeR?=			NHfKSVhCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZiMTDOUFQvOyCqYYLic5JqdmdiaX70[Ydz[XOnIFy3OG0hdXW2YX70JIlv\mWldHXkJIlvKGi3bXHuJG1VNTRiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kB3cXK3cz3pcoR2[2WmIHP5eI9x[XSqaXOg[YZn\WO2IHL5JG1VXCCjc4PhfUwhTUN3MDC9JFAvODB5IN88UU4>	NVvx[plxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUizO\|g4OTNpPkG4N\|c5PzF\|PD;hQi=>
MT4	MVXBcpRqfmm{YXygZZN{[Xl?			NYOyRZNSSW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYMTCzRkBqdm[nY4Tl[EBqdiCqdX3hckBOXDRiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kB3cXKjbD3pcoR2[2WmIHP5eI9x[XSqaXOg[YZn\WO2IHL5JG1VXCCjc4PhfUwhTUN3MDC9JFAvODB5ODFOwG0v	NHzldVg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEm1NVA6PSd-Mki5OVExQTV:L3G+
MT-4	MV\BcpRqfmm{YXygZZN{[Xl?			MWXBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKDOEIHnu[oVkfGWmIHnuJIh2dWGwIF3UMVQh[2WubIOgZpkhfHexIH\vcIQh\GmudYTpc44hdWW2aH;kJIlvKHC{ZYPlcoNmKG:oIEGwKUBHSlNuIFXDOVAhRSByLkCwPEDPxE1w	MoX5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTlzMESwNVAoRjF7MUC0NFExRC:jPh?=
MT-4	Mn;HRY51cX[rcnHsJIF{e2G7			MWHBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYhOSCQTESuN{BqdnSnZ4Lhd4UhWzJ\|MF6gcZV1[W62IHnu[oVkfGWmIHnuJIh2dWGwIF3UMVQh[2WubIOgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjD2bZJ2ey2rbnT1Z4VlKGO7dH;wZZRpcWNiZX\m[YN1KGK7IF3UWEBie3OjeTygSWM2OCB;IECuNFA6KM7:TT6=	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDN5OEexN{c,OTh\|N{i3NVM9N2F-
MT4	MXPBcpRqfmm{YXygZZN{[Xl?		MmDZOFghfG9iN{KgbJJ{	NIPVNZBCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIHnu[oVkfGWmIHnuJIh2dWGwIF3UOEBk\WyuczDlfJBz\XO\|aX7nJGdHWCCrbnP1ZoF1\WRiZn;yJFQ5KHSxIEeyJIhzeyCrbjDhZpNmdmOnIH;mJFUxLSCwb4LtZYwhcHWvYX6gd4VzfW1iYomgcZVtfGmybHWgdo92dmRidnnyZYwhemWybHnjZZRqd25ia3nu[ZRq[3NiYYPzZZktKEmSIE2gNE4xODlizszNMi=>	M1XsbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4M{m3PVY2Lz5{NkO5O\|k3PTxxYU6=
FL-4	NI\udoRCdnSrdnnyZYwh[XO\|YYm=			MmLlRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgSoVtcW6nIHntcZVvd2SnZnnjbYVv[3lidnnyeZMhcW6oZXP0[YQhcW5iY3H0JGZNNTRiY3XscJMh[XO\|ZYPz[YQh[XNidnnyZYwhWk6DIIDyc4R2[3Srb36gZpkhWlRvcWDDVkwhTUN3MDC9JFAvODB7OUig{txONg>?	NFj5bXo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEixN\|c{Oid-MkS4NVM4OzJ:L3G+
MT-4	NUWxVFJESW62aY\pdoFtKGG\|c3H5			NFvvbWNCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZiMTDSTW4hcGG{Yn;ybY5oKGmwdHXndoF{\SCpZX7lJIlv\mWldHXkJIlvKE2WLUSgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iC4aYL1d{1qdmS3Y3XkJIN6fG:yYYTobYMh\W[oZXP0JIJ6KE2WVDDhd5NigSCjZoTldkAzOCCyYYPzZYdmeyC\|ZXzlZ5Rm\CCrbjDwdoV{\W6lZTDv[kBkd22yb4Xu[EwhTUN3MDC9JFAvODFizszNMi=>	MmHwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh\|N{i3NVMoRjF6M{e4O\|E{RC:jPh?=
HeLa	Mke5RY51cX[rcnHsJIF{e2G7		MmnjOFghcHK\|	M4L0TGFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JHZUXi2JIIDz[ZVld3S7cHXkJGhKXjFibHXueIl3cXKjbDDwZZJ1cWOuZYOgbY5n\WO2ZXSgbY4hcHWvYX6gTIVN[SClZXzsd{BqdmO3YnH0[YQh\m:{IES4JIhzeyCkeTDzdIVkfHKxZnz1c5JwdWW2comsJGlEPTBiPTCwMlAyKM7:TT6=	NYDqT2dXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK4OVg{ODBpPkKyPFU5OzByPD;hQi=>
cat FL-4	MlHCRY51cX[rcnHsJIF{e2G7		NX71bXpWPyCmYYnz	MnfYRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgSoVtcW6nIHntcZVvd2SnZnnjbYVv[3lidnnyeZMhcW6oZXP0[YQhcW5iY3H0JGZNNTRiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kB3cXKjbDDy[ZBtcWOjdHnvckBi\nSncjC3JIRigXNiYomgdZVidnSrdHH0bZZmKFKWLWDDVkBidmGueYPpd{whTUN3MDC9JFAvODFizszNMi=>	NEL4NYc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUewNlg1QSd-MkW3NFI5PDl:L3G+
cat FL-4	MkXORY51cX[rcnHsJIF{e2G7		MXG3JIRigXN?	M1fMTmFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGZKXiCrbn\lZ5Rm\CCrbjDjZZQhTkxvNDDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4hfmm{YXygVm5CKGyndnXsJI1m[XO3cnXkJIFnfGW{IEeg[IF6eyCkeTDxVnQuWEOUIHHuZYx6e2m\|LDDFR\|UxKD1iMD6wNUDPxE1w	M{TzTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNzM{m1OVExLz5\|MUO5OVUyODxxYU6=
MT4	MVzBcpRqfmm{YXygZZN{[Xl?			MW\BcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYzKFKRRDCzRkBqdm[nY4Tl[EBqdiCqdX3hckBOXDRiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kB3cXKjbD3pcoR2[2WmIHP5eI9x[XSqaXOg[YZn\WO2IHL5JG1VXCCjc4PhfUwhTUN3MDC9JFAvODFzIN88UU4>	MkDJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh7NUGwPVUoRjJ6OUWxNFk2RC:jPh?=
MT4	NITBRY5CdnSrdnnyZYwh[XO\|YYm=			MYTBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDIeY1idiCrbX31co9l\W[rY3nlcoN6KH[rcoXzJFEhO0JiaX7m[YN1\WRiaX6gUXQ1KGOnbHzzJIF{e2W\|c3XkJIF{KHC{b4TlZ5Rqd25iYXfhbY5{fCC4aYL1d{1qdmS3Y3XkJIN6fG:yYYTobYMh\W[oZXP0JI1m[XO3cnXkJFUh\GG7czDwc5N1KGmwZnXjeIlwdiCkeTDNWHQh[XO\|YYmsJGVEPTBiPTCwMlAyOTdizszNMi=>	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTl2MES2Nkc,Ojl7NEC0OlI9N2F-
MT4	MoO0RY51cX[rcnHsJIF{e2G7			Mli2RY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSB\|QjDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oII\pdoFtNWmwZIXj[YQh[3m2b4DheIhq[yCnZn\lZ5QhcW5iaIXtZY4hVVR2IHPlcIx{NCCHQ{WwJF0hOC5yMUOg{txONg>?	NGrNeJE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOESxO\|M1Oid-MUi0NVc{PDJ:L3G+
MT4	M2PDVWFvfGm4aYLhcEBie3OjeR?=			MXTBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKGmwZnXjeIVlKGmwIHj1cYFvKE2WNDDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKH[rcoXzMYlv\HWlZXSgZ5l1d3CjdHjpZ{Bm\m[nY4SsJGVEPTBiPTCwMlAyOyEQvF2u	NUWx[\|h[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC2N\|A4PjVpPkKwOlMxPzZ3PD;hQi=>
MT4	NVfwSmpOSW62aY\pdoFtKGG\|c3H5			MmPWRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSB\|QjDpcoZm[3SnZDDpckBpfW2jbjDNWFQh[2WubIOgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjD2bZJ2ey2rbnT1Z4VlKGO7dH;wZZRpcWNiZX\m[YN1KGK7IF3UWEBie3OjeTygSWM2OCB;IECuNFE{KM7:TT6=	NGLMPIE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUKyO\|U2OCd-MkGyNlc2PTB:L3G+
BL21(DE3)	M3PxSmZ2dmO2aX;uJIF{e2G7		MYWxJIhz	M2n0ZWlvcGmkaYTpc44hd2ZicnXjc41jcW6jboSgTGlXNTFiaX70[Ydz[XOnIIP0ZY5lKHS{YX7z[oVzKGGldHn2bZR6KGW6cILld5Nm\CCrbjDFd4Np\XKrY3jpZUBkd2yrIFLMNlEpTEV\|KTDj[YxteyC3c3nu[{A{OlBvbHHi[Yxm\CCGTlGgd5Vje3S{YYTlJIFnfGW{IEGgbJIh[nliZHXud4l1d22ndILpZ{BidmGueYPpd{whUUN3MDC9JFAvODF\|IN88UU4>	M4DtcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NEWxO\|cyLz5{NkS1NVc4OTxxYU6=
MT-4	M1PSfWFvfGm4aYLhcEBie3OjeR?=			M{fIeWFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXiBzIF7MOE4{KGmwdHXndoF{\SCHOULRJI12fGGwdDDpcoZm[3SnZDDpckBpfW2jbjDNWE01KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[geolzfXNvaX7keYNm\CCleYTvdIF1cGmlIHXm[oVkfCCkeTDNWHQh[XO\|YYmsJGVEPTBiPTCwMlAyPSEQvF2u	NX7YbW9lRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUizO\|g4OTNpPkG4N\|c5PzF\|PD;hQi=>
MT4	MX3BcpRqfmm{YXygZZN{[Xl?		M4TLZVUh\GG7cx?=	NInRSlNCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIEPCJIlv\mWldHXkJIlvKGi3bXHuJG1VPCClZXzsd{BqdmO3YnH0[YQh\m:{IEWg[IF6eyCkeTDNWHQh[XO\|YYmsJGVEPTBiPTCwMlAyPSEQvF2u	NEHvfGg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MUOyOFU3Oid-M{GzNlQ2PjJ:L3G+
MT2	MmrIRY51cX[rcnHsJIF{e2G7			NFuzbJBCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZiaX6gUXQzKGOnbHzzJIlvKHC{ZYPlcoNmKG:oIEO1JI1oN22OIHj1cYFvKHOncoXtJIFt[nWvaX6sJGVEPTBiPTCwMlAyPiEQvF2u	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDJyN{O5PEc,OTh{MEezPVg9N2F-
MT-4	NGHlNpVCdnSrdnnyZYwh[XO\|YYm=		NH3pb4o2KGSjeYO=	MWjBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKDOEL1zBTUBqdm[nY4Tl[EBqdiCqdX3hckBOXC12IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4Yhfmm{dYOtbY5lfWOnZDDjfZRweGG2aHnjJIVn\mWldDDt[YF{fXKnZDDzeZJ3cX[jbDDh[pRmeiB3IHThfZMh[nliTWTUJIF{e2G7LDDFR\|UxKD1iMD6wNVYh\|ryPLh?=	MnfrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzMkS5NVkoRjJ2MUK0PVE6RC:jPh?=
HeLa-CD4-LTR-beta-gal	M4C4dmFvfGm4aYLhcEBie3OjeR?=		MnGyNUBl[Xl?	M2m4cGFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXi1zIEPCJIlv\mWldHXkJIlvKGi3bXHuJGhmVGFvQ1S0MWxVWi2kZYThMYdidCClZXzsd{Bi\nSncjCxJIRigSCkeTDzdIVkfHKxc3PvdIlkKGGwYXz5d4l{NCCHQ{WwJF0hOC5yMU[g{txONg>?	MmLKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4MkmyOVYoRjJ3NkK5NlU3RC:jPh?=
MT-2	MkfhRY51cX[rcnHsJIF{e2G7			NW\MSpoxSW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYMTCzRkBqdm[nY4Tl[EBqdiCqdX3hckBOXC1{IHPlcIx{KGK7IIT3c{Bnd2ymIHTpcJV1cW:wIH3leIhw\CCrbjDwdoV{\W6lZTDv[kAyOCViRlLTMEBJW0FiYX7kJIFteGijMT3BS3AtKEWFNUCgQUAxNjBzODFOwG0v	NIjCUYw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUGwOFAyOCd-MUmxNFQxOTB:L3G+
MT4	M3XSeWFvfGm4aYLhcEBie3OjeR?=			NULpUm1XSW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYMTCzRkBqdiCqdX3hckBOXDRiY3XscJMhcW5icILld4Vv[2Vib3[gNVAmKGinYYStZYN1cX[jdHXkJIZmfGGuIHLveolv\SC\|ZYL1cUwhUUN7NTC9JFAvODF7IN88UU4>	NGfENlc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEe2N\|c2OSd-MUi3OlM4PTF:L3G+
MT2	NYPkTmt5SW62aY\pdoFtKGG\|c3H5		NWOzNVlFPSCmYYnz	MYfBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKDOEIHnu[oVkfGWmIHnuJIh2dWGwIF3UNkBk\WyuczDh[pRmeiB3IHThfZMh[nliY3jlcYltfW2rbnXzZ4Vv[2ViaX6gdJJme2WwY3Wgc4YhcHWvYX6gd4VzfW1iYXzieY1qdixiRVO1NEA:KDBwMEKg{txONg>?	MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTJ6NUO4PUc,OTl{OEWzPFk9N2F-
MT4	NG\QdXVCdnSrdnnyZYwh[XO\|YYm=		NUfzOJRoPSCmYYnz	M1fnbmFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjJiUl;EJIlv\mWldHXkJIlvKGi3bXHuJG1VPCClZXzsd{BqdmO3YnH0[YQh\m:{IEWg[IF6eyCkeTDNWHQh[XO\|YYmsJGVEPTBiPTCwMlAzKM7:TT6=	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{OTN{NEW2Nkc,OzF\|MkS1OlI9N2F-
TZM-b1	NUDFbZlpSW62aY\pdoFtKGG\|c3H5		Mn73NUBpeg>?	M1Oyb2FvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXi1zIF7MOE4{KGmwZnXjeIVlKGmwIHj1cYFvKFScTT3iNUBk\WyuczDwdoV1emWjdHXkJIZweiBzIHjyJIZwdGyxd3XkJIJ6KH[rcnHsJIlv\mWldHnvckBu\WG\|dYLl[EBi\nSncjCyJIRigXNiYomgR3BTTyCjc4PhfUwhUUN3MDC9JFAvODJzIN88UU4>	NUHydJQ4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki0NFgzOjRpPkK4OFA5OjJ2PD;hQi=>
CEM-SS	NGDCV5ZCdnSrdnnyZYwh[XO\|YYm=		MoTLOkBl[Xm\|	M1zBZWFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjFiM1KgbY5n\WO2ZXSgbY4hcHWvYX6gR2VONVOVIHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDv[kB3cXK3cz3pcoR2[2WmIHP5eI9x[XSqaXOg[YZn\WO2IHHmeIVzKDZiZHH5d{BjgSCPVGOgZZN{[XluIFXDOVAhRSByLkCyN{DPxE1w	MoGwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd{OEOyOlEoRjJ5MkizNlYyRC:jPh?=
HeLa	MmL0RY51cX[rcnHsJIF{e2G7		MorGN{Bl[Xm\|	MoHhRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSB\|QjDpcoZm[3SnZDDpckBpfW2jbjDI[WxiKGOnbHzzJIV5eHKnc4PpcochS0R2LVzUVk1j\XSjLXfhcEBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJJZqemGuIILldIxq[2G2aX;uJIFnfGW{IEOg[IF6eyCkeTDy[ZBwenSncjDn[Y5mKGG\|c3H5MEBGSzVyIE2gNE4xOjN4IN88UU4>	NV\KVJN3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS2PFQzPzBpPkK0Olg1OjdyPD;hQi=>
HeLa-CD4-LTR-beta-gal	NYHSbGFZSW62aY\pdoFtKGG\|c3H5			M1\0b2FvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXi1zIEPCJIlv\mWldHXkJIlvKGi3bXHuJGhmVGFvQ1S0MWxVWi2kZYThMYdidCClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJJZqemGuIILldIxq[2G2aX;uJIJ6KFOyZXP0doFO[XhiR1XNTW5KNViVIIDsZZRmKHKnYXTldkBidmGueYPpd{whTUN3MDC9JFAvODJ\|NjFOwG0v	M{iwWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OU[xPVYxLz5{NUm2NVk3ODxxYU6=
HeLa	NYrZV4lNSW62aY\pdoFtKGG\|c3H5		NX;xR2FqOiCmYYnz	NVLGOHB{SW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYMTCzRkBqdm[nY4Tl[EBqdiCqdX3hckBJ\UyjIHPlcIx{KGW6cILld5NqdmdiQ1S0JIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[geolz[WxicnXwcIlk[XSrb36gZYZ1\XJiMjDkZZl{KGK7IHLleIEu\2GuYXP0c5Nq\GG\|ZTDy[ZBwenSncjDn[Y5mKGG\|c3H5MEBGSzVyIE2gNE4xOjRizszNMi=>	M{XIUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUK0PVE6Lz5{NEGyOFkyQTxxYU6=
MT-4	MVrBcpRqfmm{YXygZZN{[Xl?			NV31O\|FFSW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYIEGgVmlPKEiLVjCxJHJKViCqYYLic5JqdmdiaX70[Ydz[XOnIHflcoUhcW6oZXP0[YQhcW5iTWStOEBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oII\pdpV{NWmwZIXj[YQh[3m2b4DheIhq[yCnZn\lZ5Qh[nliTWTUJIF{e2G7IHHmeIVzKDRyIIDhd5Ni\2W\|IIPlcIVkfGWmIHnuJJBz\XOnbnPlJI9nKGOxbYDveY5lNCCHQ{WwJF0hOC5yMkWg{txONg>?	MoDQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh\|N{i3NVMoRjF6M{e4O\|E{RC:jPh?=
TZM-bl	NEf4VoFCdnSrdnnyZYwh[XO\|YYm=		NHHPZVI1QCCqcoO=	MWDBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDIeY1idiCrbX31co9l\W[rY3nlcoN6KH[rcoXzJFEhcW6oZXP0[YQhcW5iaIXtZY4hXFqPLXLsJINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZidnnyZYwhemWybHnjZZRqd25iYX\0[ZIhPDhiaILzJIJ6KGmwdnXyeIVlKG2rY4Lvd4NweGmlIHHuZYx6e2m\|LDDFR\|UxKD1iMD6wNlUh\|ryPLh?=	MojtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzNUS3OlIoRjJ{MUW0O\|YzRC:jPh?=
MT4	NGrmNZdHfW6ldHnvckBie3OjeR?=		MUWxJIhz	M3z4UWlvcGmkaYTpc44hd2Zid3ns[EB1gXCnIFjJWlEhO0JiaX7m[YN1\WRiaX6gbJVu[W5iTWS0JINmdGy\|IIXzbY5oKGOnbHzzJJBz\S2rbnP1ZoF1\WRid3n0bEBkd22yb4Xu[EBnd3JiMTDodkBu\WG\|dYLl[EA1KGSjeYOgdI9{fCC4aYLhcEBqdm[nY4Tpc44hcW5icILld4Vv[2Vib3[gNlAhdWdxbXygTHNCKGK7IF3UWEBie3OjeTygTWM2OCB;IECuNFI6KM7:TT6=	NF;LRXA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{Mkm2N\|E{PSd-MkK5OlMyOzV:L3G+
P4R5 MAGI	NFLIUpdCdnSrdnnyZYwh[XO\|YYm=		MVyyOEBpenN?	NFHZT2VCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIHnu[oVkfGWmIHnuJGNFPC:FWFPSOE9ES1J3IHX4dJJme3OrbnegbJVu[W5iUETSOUBOSUeLIHPlcIx{KHC{ZXnuZ5Vj[XSnZDD3bZRpKGOnbHzzJIZweiB{NDDodpMh\m:ubH;3[YQh[nlidnnyZYwhcW6oZXP0bY9vKG2nYYP1doVlKGGodHXyJFQ5KGi{czDifUBj\XSjLXfhcIFkfG:\|aXThd4UhemWyb4L0[ZIh\2WwZTDhd5NigSxiRVO1NEA:KDBwMEOg{txONg>?	NEHHWZY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MECzNVk4Pid-M{CwN\|E6PzZ:L3G+
P4R5	NEjMeZVCdnSrdnnyZYwh[XO\|YYm=		MkTLNlQhcHK\|	NEiyd2xCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIHnu[oVkfGWmIHnuJGNFPC:FWFPSOE9ES1J3IHX4dJJme3OrbnegbJVu[W5iUETSOUBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oII\pdoFtKHKncHzpZ4F1cW:wIIDy[Ylv[3WkYYTl[EB4cXSqIHPlcIx{KG[xcjCyOEBpenNiZn;scI94\WRiYomgeolz[WxiaX7m[YN1cW:wIH3lZZN2emWmIHHmeIVzKDR6IHjyd{BjgSCkZYThMYdidGGldH;zbYRie2VicnXwc5J1\XJiZ3Xu[UBie3NuIFXDOVAhRSByLkCzJO69VS5?	M3TqelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6NUK1Nlc6Lz5{OEWyOVI4QTxxYU6=
P4R5	M4TKOWFvfGm4aYLhcEBie3OjeR?=		NVLyRlNwOjRiaILz	MUTBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKGmwZnXjeIVlKGmwIHj1cYFvKFB2UkWgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKH[rcnHsJIlv\mWldHnvckBxemWrbnP1ZoF1\WRid3n0bEBk\WyuczDmc5IhOjRiaILzJIZwdGyxd3XkJIJ6KH[rcnHsJIlv\mWldHnvckBu\WG\|dYLl[EBi\nSncjC0PEBpenNiYomg[ox2d3Knc3PlcoNmKGKjc3XkJIJmfGFvZ3HsZYN1d3OrZHHz[UBz\XCxcoTldkBo\W6nIHLhd4VlKE2DR1mgZZMtKEWFNUCgQUAxNjB\|IN88UU4>	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTB\|MUC2Nkc,OjlyM{GwOlI9N2F-
P4R5	NWHRT\|FWSW62aY\pdoFtKGG\|c3H5		NFvPenozPCCqcoO=	Ml\PRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXNTFiaX7m[YN1\WRiaX6gbJVu[W5iUETSOUBk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5idnnyZYwhemWybHnjZZRqd25icILlbY5kfWKjdHXkJIZweiB{NDDodpMh\m:ubH;3[YQh[nlidnnyZYwhcW6oZXP0bY9vKGGwZDDt[YF{fXKnZDDh[pRmeiB2ODDodpMh[nliTVHHTUBie3OjeTygSWM2OCB;IECuNFMh\|ryPLh?=	NFfRfpM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEezPVgzOid-M{C3N\|k5OjJ:L3G+
P4R5	NIW4d5RCdnSrdnnyZYwh[XO\|YYm=		M{PNSFI1KGi{cx?=	NHfC[\|dCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIHnu[oVkfGWmIHnuJIh2dWGwIGC0VlUh[2WubIOgZZN{\XO\|ZXSgZZMhemWmdXP0bY9vKG:oII\pdpV{KHKncHzpZ4F1cW:wIIDy[Ylv[3WkYYTl[EB4cXSqIHPlcIx{KG[xcjCyOEBpenNiZn;scI94\WRiYomgeolz[WxiaX7m[YN1cW:wIH\vdkA1QCCqcoOgZpkhPC2vZYTofYx2dWKnbHzp[oVzgWypYXzhZ5Rwe2mmZT3iZZNm\CCPQVfJJIF{e2G7LDDFR\|UxKD1iMD6wN{DPxE1w	NVjsXGxHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkeyPFMzPjFpPkK3Nlg{OjZzPD;hQi=>
MT4	NVjG[JN3SW62aY\pdoFtKGG\|c3H5			MWrBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKDOEIHnuJIh2dWGwIF3UOEBk\WyuczDpckBxemW\|ZX7j[UBw\iB3MDWgco9zdWGuIHj1cYFvKHOncoXtMEBKSzl3IE2gNE4xOzFizszNMi=>	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDd4M{e1NUc,OTh5NkO3OVE9N2F-
MT4	MmLORY51cX[rcnHsJIF{e2G7		MornOFghfG9iN{KgbJJ{	M1vud2FvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjFiaX7m[YN1\WRiaX6gbJVu[W5iTWS0JINmdGy\|IHX4dJJme3OrbnegS2ZRKGmwY4XiZZRm\CCob4KgOFghfG9iN{KgbJJ{KGmwIIDy[ZNmdmOnIH;mJFUxLSCwb4LtZYwhcHWvYX6gd4VzfW1iYomgcZVtfGmybHWgdo92dmRidnnyZYwhemWybHnjZZRqd25ia3nu[ZRq[3NiYYPzZZktKEmSIE2gNE4xPTNizszNMi=>	MorYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ\|OUe5OlUoRjJ4M{m3PVY2RC:jPh?=
BL21(DE3)	M12wZmZ2dmO2aX;uJIF{e2G7		NWDXOmRbOSCqch?=	NXnIWYxyUW6qaXLpeIlwdiCxZjDMSWRITi:yN{Wt[IVx\W6mZX70JIZ2dGxibHXu[5RpKEiLVj2xJIlvfGWpcnHz[UBmgHC{ZYPz[YQhcW5iRYPjbIVzcWOqaXGgZ49tcSCETEKxLGRGOyliY3XscJMheHKnaX7jeYJifGWmIH\vdkAyKGi{IH\1dpRp\XJiaX7jeYJifGWmIH\vdkA6OCCvaX7zJJdqfGhiYnnveIlvNWyjYnXs[YQh\G:wb4KgSG5CKGGwZDD0ZZJo\XRiRF7BJIJ6KEiWUl[gZZN{[XluIFnDOVAhRSByLkC1PEDPxE1w	MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{OTR2Mk[4OEc,OzF2NEK2PFQ9N2F-
MT-4	NFu3blFCdnSrdnnyZYwh[XO\|YYm=			MXrBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYhOSCUSV6gTGlXKDFiUlnOJIhiemKxcnnu[{BqdnSnZ4Lhd4Uh\2WwZTDpcoZm[3SnZDDpckBOXC12IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4Yhfmm{dYOtbY5lfWOnZDDjfZRweGG2aHnjJIVn\mWldDDifUBOXFRiYYPzZZkh[W[2ZYKgOlAheGG\|c3Hn[ZMhe2WuZXP0[YQhcW5icILld4Vv[2Vib3[gZ49ueG:3bnSsJGVEPTBiPTCwMlA3QCEQvF2u	NFr5eG89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEO3PFcyOyd-MUizO\|g4OTN:L3G+
HeLaT4	M3HB[mFvfGm4aYLhcEBie3OjeR?=			MX7BcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDzbY5odGVvcn;1coQhUEmYMTDOUHgvVHW6LWKgbIFz[m:{aX7nJIlv[WO2aY\heIlv\yCvdYTheIlwdnNiaX6g[Y53NCC4cIKgZY5lKGOjcoLp[ZMh\mm{ZX\sfUBtfWOrZnXyZZNmKGenbnWgbY4heGyjY3Wgc4YhdmWoIHHzd4V{e2WmIHHzJIxmfmWuIH;mJFIhdWmwczDtZYdv\XSrYzDuZY5weGG{dHnhcJMudWWmYYTl[EBqdm[nY4Tpc44hcW5iaIXtZY4hUGWOYWS0JINmdGy\|IITy[YF1\WRiZn;yJFEtKEWFOUGgQUAxNjB5MzFOwG0v	M2TF[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzME[wNVA5Lz5{MUC2NFExQDxxYU6=
HeLa-T4	M2f4OWFvfGm4aYLhcEBie3OjeR?=		NET2do41QCCqcoO=	NXXnPZZlSW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5Qhe2mwZ3zlMZJwfW6mIFjJWlEhVky[Llz1fE1TKGijcnLvdolv\yCrbnHjeIl3[XSrbnegcZV1[XSrb37zJIlvKGWwdjygepBzKGGwZDDjZZJzcWW\|IH\pdoVndHlibIXjbYZmemG\|ZTDn[Y5mKGmwIIDsZYNmKG:oIH7l[kBqdm[nY4Tl[EBqdiCqdX3hckBJ\UyjLWS0JINmdGy\|IHHzd4V{e2WmIHHzJIx2[2moZYLhd4Uh[WO2aY\peJkh[W[2ZYKgOFghcHK\|IHL5JIV5d2enbn;1d{BTXCCjc4PhfUwhTUN3MDC9JFAvODd5IN88UU4>	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTB4MEGwPEc,OjFyNkCxNFg9N2F-
TZM-bl	NFOyOotCdnSrdnnyZYwh[XO\|YYm=		NHTkeG81QCCqcoO=	NV3MV251SW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYLUGgbY5n\WO2ZXSgbY4hcHWvYX6gWHpONWKuIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4Yhfmm{YXygdoVxdGmlYYTpc44h\m:{IES4JIhzeyCkeTDidolocHRvR3zvJIx2[2moZYLhd4Uh[XO\|YYmsJGVEPTBiPTCwMlE2KM7:TT6=	NVL1NIVjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[0PFc6OTNpPkK2OFg4QTF\|PD;hQi=>
HOS	NXH5SFdISW62aY\pdoFtKGG\|c3H5		M1\4eVMhcHK\|	NEnPV4FCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJfW2jbjDpcY12dm:mZX\pZ4lmdmO7II\pdpV{KDFiaHHyZo9zcW6pIHnueIVoemG\|ZTDONVU2UCCvdYThcpQhcW6oZXP0[YQhcW5iSF;TJINmdGy\|IIDy[Ylv[3WkYYTl[EBnd3JiMzDodpMh\m:ubH;3[YQh[nlidnnyZYwhcW6oZXP0bY9vKG2nYYP1doVlKGGodHXyJFQ5KGi{czDifUBtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZZN{[XluIFXDOVAhRSByLkG1OEDPxE1w	M1TpUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NEexPFE3Lz5{NES3NVgyPjxxYU6=
TZM-bl	NUfIOFlFSW62aY\pdoFtKGG\|c3H5			MUjBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKE6OND6zJIlv\mWldHXkJIlvKGi3bXHuJHRbVS2kbDDj[YxteyCvZXHzeZJm\CC3cITvJFI1KGi{czDifUBjemmpaISgS4xwNWy3Y3nm[ZJie2VicnXwc5J1\XJiZ3Xu[UBie3OjeTygTWM2OCB;IECuNVYh\|ryPLh?=	NVHM[Wp[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{G1OVc3ODlpPkOxOVU4PjB7PD;hQi=>
HOS	MVjBcpRqfmm{YXygZZN{[Xl?		MVizJIhzew>?	MmHTRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTJVu[W5iaX3teY5w\GWoaXPp[Y5kgSC4aYL1d{AyKGijcnLvdolv\yCrboTl[5Jie2ViWUG0N3IhdXW2YX70JIlv\mWldHXkJIlvKEiRUzDj[YxteyCycnXpcoN2[mG2ZXSg[o9zKDNiaILzJIZwdGyxd3XkJIJ6KH[rcnHsJIlv\mWldHnvckBu\WG\|dYLl[EBi\nSncjC0PEBpenNiYomgcJVkcW[ncnHz[UBz\XCxcoTldkBo\W6nIHHzd4F6NCCHQ{WwJF0hOC5zNkKg{txONg>?	NIHIZ\|M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES3NVgyPid-MkS0O\|E5OTZ:L3G+
TZM-bl	NULt[FM5SW62aY\pdoFtKGG\|c3H5		NHn3V2IyKGi{	NGrmOVhCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIF7MOE4{KGmwZnXjeIVlKGmwIHj1cYFvKFScTT3icEBk\WyuczDlfJBz\XO\|aX7nJGNZS1J2LYTyc5Bq[yCrbnP1ZoF1\WRiZn;yJFEhcHJicILpc5IhfG9iaX7m[YN1cW:wIH3lZZN2emWmIHHmeIVzKDR6IHjyd{BjgSCudXPp[oVz[XOnIILldI9zfGW{IHflcoUh[XO\|YYmsJGlEPTBiPTCwMlUh\|ryPLh?=	M{fsV\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkmxNFQzLz5{NEK5NVA1OjxxYU6=
TZM-bl	MnrKRY51cX[rcnHsJIF{e2G7		M4HWSVEhcHJ?	NUDweFJ5SW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYMTDOUFQvOyCrbn\lZ5Rm\CCrbjDoeY1idiCWWl2tZowh[2WubIOg[ZhxemW\|c3nu[{BEYEOUND30do9xcWNiaX7jeYJifGWmIH\vdkAyKGi{IIDybY9zKHSxIHnu[oVkfGmxbjDt[YF{fXKnZDDh[pRmeiB2ODDodpMh[nlibIXjbYZmemG\|ZTDy[ZBwenSncjDn[Y5mKGG\|c3H5MEBKSzVyIE2gNE42ODFzOTFOwG0v	NUH6[5V[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyPVExPDJpPkK0NlkyODR{PD;hQi=>
HeLa-T4	NWDlXWNnSW62aY\pdoFtKGG\|c3H5		NEX5boU1QCCqcoO=	NGDlPZhCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEB{cW6pbHWtdo92dmRiSFnWNUBPVFhwTIX4MXIhcGG{Yn;ybY5oKGmwYXP0bZZifGmwZzDteZRifGmxboOgbY4h\W64LDD2dJIh[W6mIHPhdpJq\XNiZnny[YZtgSCudXPp[oVz[XOnIHflcoUhcW5icHzhZ4Uhd2ZibnXmJIlv\mWldHXkJIlvKGi3bXHuJGhmVGFvVESgZ4VtdHNiYYPz[ZN{\WRiYYOgcJVkcW[ncnHz[UBi[3Srdnn0fUBi\nSncjC0PEBpenNiYomg[Zhw\2Wwb4XzJHJVKGG\|c3H5MEBGSzl3IE2gNE45OSEQvF2u	Mki2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFyNkCxNFgoRjJzME[wNVA5RC:jPh?=
HOS	M33JXWFvfGm4aYLhcEBie3OjeR?=		NEj1TVU{KGi{cx?=	M1jHemFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGh2dWGwIHntcZVvd2SnZnnjbYVv[3lidnnyeZMhOSCqYYLic5JqdmdiaX70[Ydz[XOnIFexOFBUN1FzNEjIJIRwfWKuZTDteZRidnRiaX7m[YN1\WRiaX6gTG9UKGOnbHzzJJBz\WmwY4XiZZRm\CCob4KgN{BpenNiZn;scI94\WRiYomgeolz[WxiaX7m[YN1cW:wIH3lZZN2emWmIHHmeIVzKDR6IHjyd{BjgSCudXPp[oVz[XOnIILldI9zfGW{IHflcoUh[XO\|YYmsJGVEPTBiPTCxMlkh\|ryPLh?=	MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR5MUixOkc,OjR2N{G4NVY9N2F-
MT2	MoGxRY51cX[rcnHsJIF{e2G7		MlP6N{B1dyB2IHThfZM>	MkLFRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSCQTEStN{Bp[XKkb4LpcochTzF2MGOvVVE1QEhibYX0ZY51KGmwZnXjeIVlKGmwIHj1cYFvKE2WMjDj[YxteyCvZXHzeZJm\CCjZoTldkA{KHSxIESg[IF6eyCkeTDseYNq\mW{YYPlJJJmeG:{dHXyJIdmdmViYYPzZZktKEWFNUCgQUAzNjR{IN88UU4>	NFfMO3E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MkC4NVAyOCd-M{KwPFExOTB:L3G+
HeLaT4	NV3uR2V1SW62aY\pdoFtKGG\|c3H5		Mne5NlQhcHK\|	Mn:2RY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4Sgd4lv\2ynLYLveY5lKEiLVkGgUmxZNky3eD3SJIhiemKxcnnu[{BqdmGldHn2ZZRqdmdibYX0ZZRqd26\|IHnuJIVvfixidoDyJIFv\CClYYLybYV{KG[rcnXmcJkhdHWlaX\ldoF{\SCpZX7lJIlvKHCuYXPlJI9nKG6nZjDhd5Nme3OnZDDhd{Bt\X[nbDDv[kBqdm[nY4Tpc44hfXOrbnegbJVu[W5iSHXMZXQ1KGOnbHzzJJBz\XS{ZXH0[YQh\m:{IEK0JIhzeyCob3zsc5dm\CCkeTDlfJBwe2WmIITvJJZqNCCHQ{WwJF0hPC54IN88UU4>	MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTB4MEGwPEc,OjFyNkCxNFg9N2F-
MT4	MlvRR5l1d3SxeHnjbZR6KGG\|c3H5		MXW1JIRigXN?	NFPFTFJEgXSxdH;4bYNqfHliaX6gcY9kcy2rbn\lZ5Rm\CCqdX3hckBOXDRiY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJINmdGxidnnhZoltcXS7IHnuZ5Vj[XSnZDDmc5IhPSCmYYnzJIJ6KE2WVDDhd5NigSxiQ1O1NEA:KDZwNUGg{txONg>?	MlvqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzF\|MkS1OlIoRjNzM{K0OVYzRC:jPh?=
CHO	M1HPfmZ2dmO2aX;uJIF{e2G7			MW\Jcohq[mm2aX;uJI9nKHOub4eg[IVt[XmnZDDpcpdiemRicnXjeIlngWmwZzDwc5Rie3OrdX2gZ5VzemWwdDCoTYt{MSCrbjDDbIlv\XOnIFjhcZN1\XJiT4\hdpkhMEOKTzmgZ4VtdHNiZYjwdoV{e2mwZzDoT5ZNWVRzL3jtbY5MKG2nYYP1doVlKHW\|aX7nJGlwdlexcnvzJHF2[XS2cn:gZZV1d22jdHXkJJBifGOqIHPsZY1xKHCuYYTmc5JuNCCLQ{WwJF0hOjVwMUG4PUDPxE1w	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB6N{e1N{c,OjVyOEe3OVM9N2F-
U373-MAGI	MmXBRY51cX[rcnHsJIF{e2G7	NULncHI5PTBib4KgNVAxKG6P	M3j3NlczKGi{cx?=	M{XEOWFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JHZUXi2JIIDz[ZVld3S7cHXkJGhKXi1zIF7MOE0{KGmwZnXjeIVlKGmwIHj1cYFvKFV\|N{OtUWFIUSClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25iaX6g[4FoKGyndnXsJIF1KDVyIH;yJFExOCCwTTDt[YF{fXKnZDDheEA4OiCqcoOgdI9{fCCrbn\lZ5Rqd25iYomgdXBEWiCvZYToc4Q>	NG\UV4Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{GxO\|I3OCd-MkexNVczPjB:L3G+
U373-MAGI	MYPBcpRqfmm{YXygZZN{[Xl?	NGDYeFk2OCCxcjCxNFAhdk1?	MWK3NkBpenN?	NFeycZRCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBXW1ZvRzDwd4V2\G:2eYDl[EBJUVZvMTDOUFQuOyCrbn\lZ5Rm\CCrbjDoeY1idiCXM{ezMW1CT0liY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJHU2NWejZzDs[ZZmdCCjdDC1NEBweiBzMECgcm0hdWWjc4Xy[YQh[XRiN{KgbJJ{KHCxc4SgbY5n\WO2aX;uJIJ6KHGSQ2KgcYV1cG:m	MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzFzN{K2NEc,OjdzMUeyOlA9N2F-
MT2	NWDqXI9CSW62aY\pdoFtKGG\|c3H5	Mo\TNUB2VQ>?	NF;td\|Y{OCCqcoO=	MnvrRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4Sge4lt\C22eYDlJGhKXjFiTly0MVMhcW6oZXP0[YQhcW6oZXP0[YQhcW5iaIXtZY4hVVR{IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBJUVZzIHnueIVoemG2ZXSgSG5CKGG2IEGgeW0h[W6mIH3lZZN2emWmIHHmeIVzKDNyIHjyd{Bxd3O2IHnu[oVkfGmxbjDifUBCdHVvTGTSJHBEWiCycn;0c4NwdCCkYYPl[EBu\XSqb3S=	M1fxXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyOUm2O\|gxLz5\|MEm5Olc5ODxxYU6=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	CHOP / ATF-4 / XBP-1 / Lamin B; PubMed: 24625618 PLoS One Mouse J774A.1 cells were treated with different concentrations of raltegravir (0, 5, 15, 25 or 50 µM) in the absence or presence of ritonavir (RITV, 25 µM) or thapsigargin (TG, 100 nM), a known ER stress inducer, for 4 h, and the nuclear proteins were iso䲧疝Ỵ疞㧀疜膉痘 瘿�෋ᾰƌ෋à 㺣痖帉痖Ѐ瑖堘𢡄빢᎒෋à鑸᎒彿堙奋堙巫堙᎒ﻺ᎒彿堙ﻮ᎒塚堙ﻺ᎒ꍈ堞빢᎒學堙漸堞圔堙빢᎒圞堙圭堙𢡄玚Wᾰƌ ᾰƌ戤瘯Ɖ뾠Ղ䐺痖暼瘿뾠Ղᾰƌ 뾠ՂÐ㺣痖뾠Ղ𢡄	24625618

体内研究

Raltegravir 作用于携带 SIVmac251感染的非人类灵长类动物，提高病毒-免疫。Raltegravir单独给药非人类灵长类动物后，检测不到病毒载量。^[5]

激酶实验： ^[1]	- 合并 PFV 整合实验: 为了定量分析链转移，供体DNA底物通过退火 HPLC 级寡核苷酸 5′-GACTCACTATAGGGCACGCGTCAAAATTCCATGACA 和 5′-ATTGTCATG GAATTTTGACGCGTGCCCTATAGTGAGTC而形成。反应(40 μL) 含0.75 μM PFV IN, 0.75 μM 供体 DNA, 4 nM (300 ng) 超螺旋 pGEM9-Zf(−) 靶 DNA, 125 mM NaCl, 5 mM MgSO₄, 4 μM ZnCl₂, 10 mM DTT, 0.8% (vol/vol) DMSO, 和 25 mM BisTris 丙烷–HCl, pH 7.45。加入指定浓度Raltegravir。加入2 μL PFV IN （在150 mM NaCl, 2 mM DTT, 和 10 mM Tris-HCl, pH 7.4中稀释）开始反应,在 37^oC下反应1小时后，加入25 mM EDTA 和 0.5% (wt/vol) SDS终止反应。反应产物通过与 20 μg 蛋白酶 K 在 37^oC下消化30分钟而脱蛋白，随后使用乙醇沉淀,在在1.5％琼脂糖凝胶上分离，然后通过用溴化乙锭染色观察。通过实时定量PCR, 使用 Platinum SYBR Green qPCR SuperMix 和三种引物 : 5′-CTACTTACTCTAGCTTCCCGGCAAC, 5′-TTCGCCAGTTAATAGTTTGCGCAAC, 和 5′-GACTCACTATAGGGCACGCGT定量分析整合产物。PCR 反应 (20 μL) 含0.5 μM 每种引物和1 μL 稀释的整合反应产物。在95^oC下进行5分钟变性，在CFX96 PCR仪上进行35次循环，再在95^oC下变性10秒，在56^oC下退火30秒，在68^oC下延伸1分钟。在INSTI存在时，使用连续稀释的WT PFV IN 反应，获得标准曲线。
细胞实验： ^[5]	- 合并 Cell lines: 人类MT-4 细胞 Concentrations: 0.0001 μM -1 μM Incubation Time: 2小时 Method: 使用 SIVmac251, HIV-1 (IIIB) 和 HIV-2 (CDC 77618)对人类MT-4细胞进行多重感染2小时。然后在PBS中冲洗细胞3次，在有或无一系列一式三份Raltegravir 浓度 (0.0001 μM -1 μM)时，按5 × 10⁵/mL 悬浮在含新鲜培养基 (在原代细胞中加入 50 单位/mL IL-2 ) 的96孔板中。也制备未治疗的感染对照和模拟感染对照，用于比较不同处理法得到的实验数据。通过MTT法(MT-4/MTT实验 )定量分析致MT-4细胞死亡的病毒。显微镜检测发现病毒感染的细胞培养物由于缺乏成簇的能力而大量死亡。移液打断成簇，在 37^oC下温育2小时后, 通过光学显微镜l (100 × 放大倍数)观察新簇形成。通过ELISA收集细胞培养上清液，用于测量HIV-1 p24 和 HIV-2/SIVmac251 p27核心抗原。在CEMx174感染的细胞培养物中，具有病毒包膜糖蛋白诱导形成多核体的倾向,按盲实验形式计数多核体，感染5天后，通过光学显微镜观察每孔。 (Only for Reference)
动物实验： ^[5]	- 合并 Animal Models: 印度猕猴 Dosages: 50 mg/kg 或 100 mg/kg, 每天两次 Administration: 口服处理 (Only for Reference)

参考文献

- 合并

溶解度 (25°C)

体外	DMSO	88 mg/mL (198.01 mM)
	Water	Insoluble
	Ethanol	Insoluble
体内	从左到右依次将纯溶剂加入产品，现配现用(数据来自Selleck实验检测而非文献)： 2% DMSO+40% PEG 300+2% Tween 80+ddH2O	8mg/mL

* 溶解度检测是由Selleck技术部门检测的，可能会和文献中提供的溶解度有所差异，这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据 Download Raltegravir (MK-0518) SDF

分子量	444.42
化学式	C₂₀H₂₁FN₆O₅
CAS号	518048-05-0
储存条件	3年-20°C 粉状 2年-80°C 溶于溶剂
别名	N/A

动物体内配方计算器 (澄清溶液)

第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）

给药剂量

mg/kg

动物平均体重

每只动物给药体积

动物数量

只

第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）

% DMSO+ % + % Tween 80+ % ddH₂O

计算重置

计算结果:

工作液浓度： mg/ml；

DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；

体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH₂O，混匀澄清。

注意：1. 首先保证母液是澄清的；
2. 一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。

计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

质量

浓度

体积

分子量
=

×

×

*在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。

稀释计算器

用本工具协助配置特定浓度的溶液，使用的计算公式为：

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入输出 )

C1

V1

C2

V2
×

=

×

在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.

连续稀释计算器方程

连续稀释
初始浓度:
稀释倍数:

计算结果

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

分子量计算器

通过输入化合物的化学式来计算其分子量：

注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量	浓度	体积	分子量
=	×	×
计算

临床试验信息 (data from https://clinicaltrials.gov, updated on 2021-05-17)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04513626	Recruiting	Drug: DORAVIRINE 100 MG [Pifeltro]	HIV Infections	Centre de Recherches et d''Etude sur la Pathologie Tropicale et le Sida	September 15 2020	Phase 2
NCT03667547	Completed	Drug: Raltegravir	Human Immunodeficiency Virus (HIV) Infection	Merck Sharp & Dohme Corp.	September 27 2018	Phase 4
NCT03174977	Recruiting	Drug: 18F-Raltegravir	HIV-1-infection	University of California San Francisco\|Merck Sharp & Dohme Corp.	April 1 2018	Early Phase 1
NCT03205566	Completed	Drug: Raltegravir 400Mg Tab\|Drug: Lamivudine 150Mg Tablet	Hiv	Guy''s and St Thomas'' NHS Foundation Trust	September 19 2017	Phase 4

技术支持

在订购、运输、储存和使用我们的产品的任何阶段，您遇到的任何问题，均可以通过拨打我们的热线电话400-668-6834，或者技术支持邮箱tech@selleck.cn，直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题，请给我们留言。

研究领域

产品类型

定制您的化合物库

Raltegravir (MK-0518)

客户使用Selleck生产的Raltegravir (MK-0518)发表文献46篇：

产品安全说明书

Integrase抑制剂选择性比较

生物活性

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

参考文献

溶解度 (25°C)

化学数据 Download Raltegravir (MK-0518) SDF

动物体内配方计算器 (澄清溶液)

计算器

摩尔浓度计算器

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

稀释计算器

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

连续稀释计算器方程

连续稀释

计算结果

分子量计算器

总分子量：g/mol

摩尔浓度计算器

临床试验信息 (data from https://clinicaltrials.gov, updated on 2021-05-17)

技术支持

Integrase Signaling Pathway Map

相关Integrase产品