Towards irreversible HIV inactivation: stable gp120 binding by nucleophilic antibodies |
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Authors: | Nishiyama Yasuhiro Karle Sangeeta Mitsuda Yukie Taguchi Hiroaki Planque Stephanie Salas Maria Hanson Carl Paul Sudhir |
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Affiliation: | Chemical Immunology and Therapeutics Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030, USA. |
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Abstract: | 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(1/2) 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. |
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Keywords: | nucleophilic antibody gp120 HIV |
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