Blocking HIV-1 entry by a gp120 surface binding inhibitor

被引：17

作者：

Tsou, Lun K. ^{[2
]}

Chen, Chin-Ho ^{[3
]}

Dutschman, Ginger E. ^{[1
]}

Cheng, Yung-Chi ^{[1
]}

Hamilton, Andrew D. ^{[2
,4
]}

机构：

[1] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA

[2] Yale Univ, Dept Chem, New Haven, CT 06520 USA

[3] Duke Univ, Med Ctr, Surg Oncol Res Facil, Durham, NC 27710 USA

[4] Univ Oxford, Dept Chem, Oxford OX1 2JD, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 09期

基金：

美国国家卫生研究院;

关键词：

Calix[4]arene scaffold; HIV-entry inhibitor; Proteomimetic inhibitor; Protein surface recognition; IMMUNODEFICIENCY-VIRUS TYPE-1; CD4; RECEPTOR-BINDING; SYNTHETIC MOLECULE; GROWTH-FACTOR; IN-VITRO; ENVELOPE; DRUG; TUMORIGENESIS; ANGIOGENESIS; RESISTANCE;

D O I：

10.1016/j.bmcl.2012.02.079

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report the mode of action of a proteomimetic compound that binds to the exterior surface of gp120 and blocks HIV-1 entry into cells. Using a one cycle time-of-addition study and antibody competition binding studies, we have determined that the compound blocks HIV-1 entry through modulation of key protein-protein interactions mediated by gp120. The compound exhibits anti-HIV-1 replication activities against several pseudotype viruses derived from primary isolates and the resistant strains isolated from existing drug candidates with equal potency. Together, these data provide evidence that the proteomimetic compound represents a novel class of HIV-1 viral entry inhibitor that functions through protein surface recognition in analogy to an antibody. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：3358 / 3361

页数：4

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