Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus.

Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus. Research Abstract Details 

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Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus. Abstract Text:

Hui Xie,Danny Ng,Sergey N Savinov,Barna Dey,Peter D Kwong,Richard Wyatt,Amos B Smith,Wayne A Hendrickson,

The first step in HIV infection is the binding of the envelope glycoprotein gp120 to the host cell receptor CD4. An interfacial "Phe43 cavity" in gp120, adjacent to residue Phe43 of gp120-bound CD4, has been suggested as a potential target for therapeutic intervention. We designed a CD4 mutant (D1D2F43C) for site-specific coupling of compounds for screening against the cavity. Altogether, 81 cysteine-reactive compounds were designed, synthesized, and tested. Eight derivatives exceeded the affinity of native D1D2 for gp120. Structure-activity relationships (SAR) for derivatized CD4 binding to gp120 revealed significant plasticity of the Phe43 cavity and a narrow entrance. The primary contacts for compound recognition inside the cavity were found to be van der Waals interactions, whereas hydrophilic interactions were detected in the entrance. This first SAR on ligand binding to an interior cavity of gp120 may provide a starting point for structure-based assembly of small molecules targeting gp120-CD4 interaction.

Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus. Publishing Authors By Initials

H Xie,D Ng,SN Savinov,B Dey,PD Kwong,R Wyatt,AB Smith,WA Hendrickson,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: structure-activity relationship research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: structure-activity relationship research

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Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of medicinal chemistry

VOLUME: 50

Page Numbers: 4898-908

Journal Abbreviation: J. Med. Chem.

ISSN: 0022-2623

DAY: 6

MONTH: 09

YEAR: 2007

Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9716531

Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus. Keywords Mesh Terms:

KEYWORDS: Structure-Activity Relationship

MESH TERMS: metabolism

Chemical & Substance for Abstract: Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus. Information

Substance Name: Ligands

Registry Number: 0

Grant and Affiliation Information for Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus.

AFFILIATION: Department of Pharmacology and Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: P01-GM 056550

ACRONYM: GM

MEDLINETA: J Med Chem

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