Blocking HIV-1 entry by a gp120 surface binding inhibitor

Lun K. Tsou; Chin Ho Chen; Ginger E. Dutschman; Yung Chi Cheng; Andrew D. Hamilton

doi:10.1016/j.bmcl.2012.02.079

Blocking HIV-1 entry by a gp120 surface binding inhibitor

Lun K. Tsou, Chin Ho Chen, Ginger E. Dutschman, Yung Chi Cheng, Andrew D. Hamilton

Chemistry

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

Abstract

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.

Original language	English (US)
Pages (from-to)	3358-3361
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	9
DOIs	https://doi.org/10.1016/j.bmcl.2012.02.079
State	Published - May 1 2012

Keywords

Calix[4]arene scaffold
HIV-entry inhibitor
Protein surface recognition
Proteomimetic inhibitor

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.2012.02.079

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abstract = "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.",

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AU - Chen, Chin Ho

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AU - Cheng, Yung Chi

AU - Hamilton, Andrew D.

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AB - 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.

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Blocking HIV-1 entry by a gp120 surface binding inhibitor

Abstract

Keywords

ASJC Scopus subject areas

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