Probing of CD4 binding pocket of HIV-1 gp120 glycoprotein using unnatural phenylalanine analogues

Xiaobo Yu; Poulami Talukder; Chandrabali Bhattacharya; Nour Eddine Fahmi; Jamie A. Lines; Larisa Dedkova; Joshua LaBaer; Sidney Hecht; Shengxi Chen

doi:10.1016/j.bmcl.2014.10.058

Probing of CD4 binding pocket of HIV-1 gp120 glycoprotein using unnatural phenylalanine analogues

Xiaobo Yu, Poulami Talukder, Chandrabali Bhattacharya, Nour Eddine Fahmi, Jamie A. Lines, Larisa Dedkova, Joshua LaBaer, Sidney Hecht, Shengxi Chen

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

CD4-gp120 interaction is the first step for HIV-1 entry into host cells. A highly conserved pocket in gp120 protein is an attractive target for developing gp120 inhibitors or novel HIV detection tools. Here we incorporate seven phenylalanine derivatives having different sizes and steric conformations into position 43 of domain 1 of CD4 (mD1.2) to explore the architecture of the 'Phe43 cavity' of HIV-1 gp120. The results show that the conserved hydrophobic pocket in gp120 tolerates a hydrophobic side chain of residue 43 of CD protein, which is 12.2 Å in length and 8.0 Å in width. This result provides useful information for developing novel gp120 inhibitors or new HIV detection tools.

Original language	English (US)
Pages (from-to)	5699-5703
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	24
DOIs	https://doi.org/10.1016/j.bmcl.2014.10.058
State	Published - Dec 15 2014

Keywords

CD4
Keyword HIV-1 gp120
Microarray
Phe43 cavity
Phenylalanine derivatives

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2014.10.058

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title = "Probing of CD4 binding pocket of HIV-1 gp120 glycoprotein using unnatural phenylalanine analogues",

abstract = "CD4-gp120 interaction is the first step for HIV-1 entry into host cells. A highly conserved pocket in gp120 protein is an attractive target for developing gp120 inhibitors or novel HIV detection tools. Here we incorporate seven phenylalanine derivatives having different sizes and steric conformations into position 43 of domain 1 of CD4 (mD1.2) to explore the architecture of the 'Phe43 cavity' of HIV-1 gp120. The results show that the conserved hydrophobic pocket in gp120 tolerates a hydrophobic side chain of residue 43 of CD protein, which is 12.2 {\AA} in length and 8.0 {\AA} in width. This result provides useful information for developing novel gp120 inhibitors or new HIV detection tools.",

keywords = "CD4, Keyword HIV-1 gp120, Microarray, Phe43 cavity, Phenylalanine derivatives",

author = "Xiaobo Yu and Poulami Talukder and Chandrabali Bhattacharya and Fahmi, {Nour Eddine} and Lines, {Jamie A.} and Larisa Dedkova and Joshua LaBaer and Sidney Hecht and Shengxi Chen",

note = "Funding Information: The authors thank Dr. Dimiter S. Dimitrov for the mD1.2 plasmid as a gift. The authors also appreciate the help from Dr. Weizao Chen in the Center of Cancer Research of the National Cancer Institute during the construction of the new plasmid. This work was performed with the support of the Bill & Melinda Gates Foundation through the Grant Challenges Explorations initiative (Grant No. OPP1061337 ). Publisher Copyright: {\textcopyright} Published by Elsevier Ltd.",

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AU - Yu, Xiaobo

AU - Talukder, Poulami

AU - Bhattacharya, Chandrabali

AU - Fahmi, Nour Eddine

AU - Lines, Jamie A.

AU - Dedkova, Larisa

AU - LaBaer, Joshua

AU - Hecht, Sidney

AU - Chen, Shengxi

N1 - Funding Information: The authors thank Dr. Dimiter S. Dimitrov for the mD1.2 plasmid as a gift. The authors also appreciate the help from Dr. Weizao Chen in the Center of Cancer Research of the National Cancer Institute during the construction of the new plasmid. This work was performed with the support of the Bill & Melinda Gates Foundation through the Grant Challenges Explorations initiative (Grant No. OPP1061337 ). Publisher Copyright: © Published by Elsevier Ltd.

PY - 2014/12/15

Y1 - 2014/12/15

N2 - CD4-gp120 interaction is the first step for HIV-1 entry into host cells. A highly conserved pocket in gp120 protein is an attractive target for developing gp120 inhibitors or novel HIV detection tools. Here we incorporate seven phenylalanine derivatives having different sizes and steric conformations into position 43 of domain 1 of CD4 (mD1.2) to explore the architecture of the 'Phe43 cavity' of HIV-1 gp120. The results show that the conserved hydrophobic pocket in gp120 tolerates a hydrophobic side chain of residue 43 of CD protein, which is 12.2 Å in length and 8.0 Å in width. This result provides useful information for developing novel gp120 inhibitors or new HIV detection tools.

AB - CD4-gp120 interaction is the first step for HIV-1 entry into host cells. A highly conserved pocket in gp120 protein is an attractive target for developing gp120 inhibitors or novel HIV detection tools. Here we incorporate seven phenylalanine derivatives having different sizes and steric conformations into position 43 of domain 1 of CD4 (mD1.2) to explore the architecture of the 'Phe43 cavity' of HIV-1 gp120. The results show that the conserved hydrophobic pocket in gp120 tolerates a hydrophobic side chain of residue 43 of CD protein, which is 12.2 Å in length and 8.0 Å in width. This result provides useful information for developing novel gp120 inhibitors or new HIV detection tools.

KW - CD4

KW - Keyword HIV-1 gp120

KW - Microarray

KW - Phe43 cavity

KW - Phenylalanine derivatives

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Probing of CD4 binding pocket of HIV-1 gp120 glycoprotein using unnatural phenylalanine analogues

Abstract

Keywords

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