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Towards biomolecular assembly employing extended native chemical ligation in combination with thioester synthesis using an N→S acyl shift
Author(s) -
Ackrill Tom,
Anderson David W.,
Macmillan Derek
Publication year - 2010
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21473
Subject(s) - thioester , native chemical ligation , chemistry , cysteine , chemical ligation , residue (chemistry) , thiol , reactivity (psychology) , peptide , ligation , stereochemistry , combinatorial chemistry , lipid anchored protein , thiazolidine , biochemistry , enzyme , medicine , apoptosis , alternative medicine , microbiology and biotechnology , pathology , autophagy , biology
The advent of kinetically controlled Native Chemical Ligation has permitted more efficient sequential Native Chemical Ligation reactions to take place in one pot where one or more of the peptide fragments contains an N‐terminal cysteine residue and a C‐terminal thioester. The reactivity of the thioester component can dictate how fragments behave through careful choice of leaving group (alkyl or aryl thiol) and the C‐terminal amino acid residue. Although thioester reactivity is exquisitely controlled, reactivity of the N‐terminal cysteine residue has been curbed using protecting groups, usually the thiazolidine‐4‐carboxo (Thz) group as it can be removed in the presence of the thioester at acidic pH. Only recently has the concept of orthogonal ligation been extended to thiol auxiliary mediated Native Chemical Ligation (a.k.a. Extended Ligation) which, owing to their inherent difference in reactivity, have allowed peptides to be selectively extended at the C‐terminus without recourse to protecting groups on the N‐terminus. Herein we explored the compatibility of acyl transfer auxiliaries with peptide thioester production via an N → S acyl shift for this purpose. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 495–503, 2010.