Multivalent Conjugates of Poly-γ-d-glutamic Acid from Bacillus licheniformis with Antibody F(ab‘) and Glycopeptide Ligands

Poly-γ-d-glutamic acid from Bacillus licheniformis is a water-soluble, nontoxic, nonimmunogenic exopolymer. Using synthetic linkers, the α-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.