Multivalent conjugates of poly-?-D-glutamic acid from Bacillus licheniformis with antibody F(ab') and glycopeptide ligands

Prodhomme, Emmanuel J.F., Tutt, Alison L., Glennie, Martin J. and Bugg, Timothy D.H. (2003) Multivalent conjugates of poly-?-D-glutamic acid from Bacillus licheniformis with antibody F(ab') and glycopeptide ligands. Bioconjugate Chemistry, 14 (6), 1148-1155. (doi:10.1021/bc020019m S1043-1802(02)00019-8).

Abstract

Poly--D-glutamic acid from Bacillus licheniformis is a water-soluble, nontoxic, nonimmunogenic exopolymer. Using synthetic linkers, the -carboxylate side chains of PGA were conjugated to an exposed thiol side chain of an antibody F(ab') fragment, Mc109F4. Analysis of the PGA-Mc109F4 conjugate by gel filtration HPLC revealed a mixture of multivalent conjugates. The PGA-Mc109F4 conjugate retained biological activity, but showed a lower binding affinity to target BCL3B3 cells than free Mc109F4 F(ab')2 by flow cytometry, and a lower efficacy for BCL3B3 growth inhibition than free Mc109F4 F(ab')2. PGA was also conjugated with the free amino group of glycopeptide antibiotic vancomycin. The PGA-vancomycin conjugate showed slightly lower antibacterial activity than free vancomycin versus susceptible Bacillus subtilis, but slightly higher activity versus intrinsically resistant Leuconostoc mesenteroides.

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