Multivalent conjugates of poly-gamma-D-glutamic acid from Bacillus licheniformis with antibody F(ab') and glycopeptide ligands.
Poly-gamma-D-glutamic acid from Bacillus licheniformis is a water-soluble, nontoxic, nonimmunogenic exopolymer. Using synthetic linkers, the alpha-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.
Prodhomme
Emmanuel J F
EJ
Department of Chemistry, University of Warwick, Coventry, UK.
Tutt
Alison L
AL
Glennie
Martin J
MJ
Bugg
Timothy D H
TD
D000912:Antibodies, Neoplasm / Q000737:chemistry / Q000276:immunology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001407:Bacillus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D006020:Glycopeptides / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000494:pharmacology; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000276:immunology; D008024:Ligands; D016393:Lymphoma, B-Cell / Q000276:immunology; D015394:Molecular Structure; D011099:Polyglutamic Acid / Q000737:chemistry* / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology
D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D006020:Glycopeptides; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D008024:Ligands; D011099:Polyglutamic Acid; D014640:Vancomycin