Bart Hoorelbeke, Youngju Kim, Toshikazu Oki, Yasuhiro Igarashi and Jan Balzarini Pages 1907 - 1915 ( 9 )
Pradimicins (PRM) are a unique class of nonpeptidic carbohydrate-binding agents that inhibit HIV infection by efficiently binding to the HIV-1 envelope gp120 glycans in the obligatory presence of Ca2+. Surface plasmon resonance (SPR) data revealed that addition of EDTA dose-dependently results in lower binding signals of PRM-A to immobilized gp120. Pradimicin derivatives that lack the free carboxylic acid group on the C-18 position failed to bind gp120 and were devoid of significant antiviral activity. Ca2+ was much more efficient for PRM-A binding to gp120 than Cd2+, Ba2+ or Sr2+. Instead, calcium could not be replaced by any other mono- (i.e. K+), di- (i.e. Cu2+, Mg2+, Mn2+, Fe2+, Zn2+) or trivalent (i.e. Al,sup>3+, Fe3+) cation without complete loss of gp120 binding. However, Zn2+, Mg2+ and Mn2+ added to a Ca2+- pradimicin mixture, prevented pradimicin from efficient binding to gp120 glycans. These data suggest that these bivalent cations may bind to pradimicins but lead to pradimicin-cation complexes that are unable to further coordinate with the glycans of gp120. Thus, in order to afford antiviral activity, only a few cations can (i) bind to pradimicin to form a dimeric complex and (ii) subsequently coordinate the pradimicin/cation interaction with gp120 glycans
carbohydrate-binding agent (CBA), cation complexes, glycans, HIV envelope gp120, pradimicin, surface plasmon resonance (SPR).
Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.