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Towards irreversible HIV inactivation: stable gp120 binding by nucleophilic antibodies
Author(s) -
Nishiyama Yasuhiro,
Karle Sangeeta,
Mitsuda Yukie,
Taguchi Hiroaki,
Planque Stephanie,
Salas Maria,
Hanson Carl,
Paul Sudhir
Publication year - 2006
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.795
Subject(s) - human immunodeficiency virus (hiv) , antibody , chemistry , nucleophile , biophysics , combinatorial chemistry , biochemistry , virology , medicine , immunology , biology , catalysis
Conventional antibodies react with antigens reversibly. We report the formation of unusually stable complexes of HIV gp120 and nucleophilic antibodies raised by immunization with an electrophilic HIV gp120 analog (E‐gp120). The stability of the complexes was evident from their very slow dissociation in a nondenaturing solvent (approximate t ½ 18.5 days) and their resistance to dissociation by a denaturant commonly employed to disrupt noncovalent protein–protein binding (sodium dodecyl sulfate). Kinetic studies indicated time‐dependent and virtually complete progression of the antibody‐gp120 complexes from the initial noncovalent state to a poorly dissociable state. The antibodies to E‐gp120 displayed improved covalent reactivity with an electrophilic phosphonate probe compared to control antibodies, suggesting their enhanced nucleophilicity. One of the stably binding antibodies neutralized the infectivity of CCR5‐dependent primary HIV strains belonging to clades B and C. These findings suggest the feasibility of raising antibodies capable of long‐lasting inactivation of antigens by electrophilic immunization. Copyright © 2006 John Wiley & Sons, Ltd.