Chemically programmed antibodies as HIV-1 attachment Inhibitors

Shinichi Sato; Tsubasa Inokuma; Nobumasa Otsubo; Dennis R. Burton; Carlos F. Barbas

doi:10.1021/ml400097z

Chemically programmed antibodies as HIV-1 attachment Inhibitors

Shinichi Sato, Tsubasa Inokuma, Nobumasa Otsubo, Dennis R. Burton, Carlos F. Barbas

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

16 Citations (Scopus)

Abstract

Herein, we describe the design and application of two small-molecule anti-HIV compounds for the creation of chemically programmed antibodies. N-Acyl-β-lactam derivatives of two previously described molecules BMS-378806 and BMS-488043 that inhibit the interaction between HIV-1 gp120 and T-cells were synthesized and used to program the binding activity of aldolase antibody 38C2. Discovery of a successful linkage site to BMS-488043 allowed for the synthesis of chemically programmed antibodies with affinity for HIV-1 gp120 and potent HIV-1 neutralization activity. Derivation of a successful conjugation strategy for this family of HIV-1 entry inhibitors enables its application in chemically programmed antibodies and vaccines and may facilitate the development of novel bispecific antibodies and topical microbicides.

Original language	English
Pages (from-to)	460-465
Number of pages	6
Journal	ACS Medicinal Chemistry Letters
Volume	4
Issue number	5
DOIs	https://doi.org/10.1021/ml400097z
Publication status	Published - 2013 May 9
Externally published	Yes

Keywords

Bioconjugation
anti-HIV agent
chemically programmed antibody
entry inhibitor
microbicide

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/ml400097z

Cite this

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title = "Chemically programmed antibodies as HIV-1 attachment Inhibitors",

abstract = "Herein, we describe the design and application of two small-molecule anti-HIV compounds for the creation of chemically programmed antibodies. N-Acyl-β-lactam derivatives of two previously described molecules BMS-378806 and BMS-488043 that inhibit the interaction between HIV-1 gp120 and T-cells were synthesized and used to program the binding activity of aldolase antibody 38C2. Discovery of a successful linkage site to BMS-488043 allowed for the synthesis of chemically programmed antibodies with affinity for HIV-1 gp120 and potent HIV-1 neutralization activity. Derivation of a successful conjugation strategy for this family of HIV-1 entry inhibitors enables its application in chemically programmed antibodies and vaccines and may facilitate the development of novel bispecific antibodies and topical microbicides.",

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doi = "10.1021/ml400097z",

language = "English",

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T1 - Chemically programmed antibodies as HIV-1 attachment Inhibitors

AU - Sato, Shinichi

AU - Inokuma, Tsubasa

AU - Otsubo, Nobumasa

AU - Burton, Dennis R.

AU - Barbas, Carlos F.

PY - 2013/5/9

Y1 - 2013/5/9

N2 - Herein, we describe the design and application of two small-molecule anti-HIV compounds for the creation of chemically programmed antibodies. N-Acyl-β-lactam derivatives of two previously described molecules BMS-378806 and BMS-488043 that inhibit the interaction between HIV-1 gp120 and T-cells were synthesized and used to program the binding activity of aldolase antibody 38C2. Discovery of a successful linkage site to BMS-488043 allowed for the synthesis of chemically programmed antibodies with affinity for HIV-1 gp120 and potent HIV-1 neutralization activity. Derivation of a successful conjugation strategy for this family of HIV-1 entry inhibitors enables its application in chemically programmed antibodies and vaccines and may facilitate the development of novel bispecific antibodies and topical microbicides.

AB - Herein, we describe the design and application of two small-molecule anti-HIV compounds for the creation of chemically programmed antibodies. N-Acyl-β-lactam derivatives of two previously described molecules BMS-378806 and BMS-488043 that inhibit the interaction between HIV-1 gp120 and T-cells were synthesized and used to program the binding activity of aldolase antibody 38C2. Discovery of a successful linkage site to BMS-488043 allowed for the synthesis of chemically programmed antibodies with affinity for HIV-1 gp120 and potent HIV-1 neutralization activity. Derivation of a successful conjugation strategy for this family of HIV-1 entry inhibitors enables its application in chemically programmed antibodies and vaccines and may facilitate the development of novel bispecific antibodies and topical microbicides.

KW - Bioconjugation

KW - anti-HIV agent

KW - chemically programmed antibody

KW - entry inhibitor

KW - microbicide

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JF - ACS Medicinal Chemistry Letters

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Chemically programmed antibodies as HIV-1 attachment Inhibitors

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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