Print Email Facebook Twitter Mechanism of anti-HIV activity of succinylated human serum albumin Title Mechanism of anti-HIV activity of succinylated human serum albumin Author Kuipers, M.E. Berg, M.V.D. Meijer, D.K.F. Huisman, H. TNO Preventie en Gezondheid Publication year 1999 Abstract In the present study, we described the interaction of succinylated human serum albumin (Suc-HSA), a negatively charged anti-HIV-1 active protein, with HIV-1 gp120 and in detail with the third variable domain of gp120 (V3 loop). To this end, different assay formats were tested in which gp120- and V3-related peptides were presented in various configurations in order to investigate the effect of the conformational structure of the V3 loop on the interaction with negatively charged albumins. When gp120 presented via a lectin was used, it was observed that Suc-HSA bound to native gp120. The binding site appeared to be located at or near the thrombin digestion site (GPGRAF sequence) in the V3 loop of gp120, since the cleavage of the loop resulted in decreased binding of Suc-HSA. In addition, Suc-HSA was able to protect the V3 region of gp120 from cleaving with thrombin. In contrast, significant binding of Suc-HSA to V3 loop or gp120 peptides was not observed when both were presented in a fluid phase system, suggesting the involvement of a monovalent-low affinity binding of Suc-HSA. Using overlapping peptides delineating the whole V3 loop immobilized to CNBr-Sepharose, we noticed that the interaction of the V3 loop with Suc-HSA was predominantly induced by electrostatic interactions between positively charged linearized peptide fragments and Suc-HSA and was positively influenced by the presence of hydrophobic amino in the V3 loop fragments as well. Moreover, the highest affinity site was located at sites near the GPGRAF sequence. These observations add to the evidence, collected earlier, that Suc-HSA interferes at the level of virus entry, independent of interaction with the CD4 receptor. Since the recently discovered chemokine receptors are negatively charged, we can hypothesize that Suc-HSA is able to prevent the positively charged V3 loop from interacting with these types of receptors, thereby inhibiting virus entry. Copyright (C) 1999 Elsevier Science Inc. Subject BiologyBinding studiesgp120 peptidesHIV-1PolyanionV3 loop peptidesAmino Acid SequenceAnti-HIV AgentsBinding SitesCell LineHIV Envelope Protein gp120HIV-1HumansImmunoblottingMolecular Sequence DataPeptide FragmentsProtein ConformationSepharoseSequence Homology, Amino AcidSerum Albumin To reference this document use: http://resolver.tudelft.nl/uuid:61c4a62d-2ebe-42b2-a75a-ff98603e8fa9 DOI https://doi.org/10.1016/s0006-2952(98)00369-4 TNO identifier 235003 ISSN 0006-2952 Source Biochemical Pharmacology, 57 (8), 889-898 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.