THE DESIGN, SYNTHESIS, AND INITIAL EVALUATION OF BENZOPHENONE-CONTAINING PEPTIDES AS POTENTIAL PHOTOAFFINITY LABELS OF OLIGOSACCHARYLTRANSFERASE

The benzophenone photophore was incorporated into protected tripeptide s and tetrapeptides as photoactivatable probes to study the multimeric enzyme oligosaccharyltransferase (OST). These peptides contain the -A sn-X-Thr- sequon which is required for OST-catalyzed N-glycosylation. Two tripeptides, Bz-Asn-Bpa-Thr-NH2 (3b) and Bz-Asn-Lys[N-epsilon-(4-B z)Bz]-Thr-NH2 (4b), were found to be good OST substrates. They were co mpetitive inhibitors versus standard peptide substrate [C-14]Bz-Asn-Le u-Thr-NH2 and their K-i values were determined to be 41 +/- 61 mu M an d 21 +/- 6 mu M, respectively, using synthetic (GlcNAc)(2)-PP-dolichol .. (C) 1998 Elsevier Science Ltd. All rights reserved.