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 |
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Pages (from-to) | 460-465 |
Number of pages | 6 |
Journal | ACS Medicinal Chemistry Letters |
Volume | 4 |
Issue number | 5 |
DOIs | |
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