6u85

Publication Abstract from PubMed

By exploiting a uniquely reactive lysine residue (Lys99) for site-specific attachment of small molecules, the humanized catalytic antibody h38C2 has been used as bioconjugation module in the assembly of chemically programmed antibodies and antibody-drug conjugates. Treatment of h38C2 with beta-lactam-functionalized small molecules has been previously shown to result in covalent conjugation by selective formation of a stable amide bond with the epsilon-amino group of the Lys99 residue. Here we report that heteroaryl methylsulfonyl (MS-PODA)-functionalized small molecules represent an alternative bioconjugation strategy through highly efficient, site-specific, and stable arylation of the Lys99 residue. A set of chemically programmed antibodies and antibody-drug conjugates assembled by Lys99 arylation provided proof-of-concept for the therapeutic utility of this alternative bioconjugation strategy. While being equally effective as beta-lactam-functionalized ligands for bioconjugation with catalytic antibody h38C2, the MS-PODA moiety offers distinct synthetic advantages, making it highly attractive.

Site-Specific Lysine Arylation as an Alternative Bioconjugation Strategy for Chemically Programmed Antibodies and Antibody-Drug Conjugates.,Hwang D, Tsuji K, Park H, Burke TR Jr, Rader C Bioconjug Chem. 2019 Nov 1. doi: 10.1021/acs.bioconjchem.9b00609. PMID:31675216^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.