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.
authors.affiliation: Department of Molecular Biology and Chemistry and the Skaggs Institute for Chemical Biology and Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Inokuma
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Otsubo
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Barbas
keywords: anti-HIV agent; bioconjugation; chemically programmed antibody; entry inhibitor; microbicide