Towards biomolecular assembly employing extended native chemical ligation in combination with thioester synthesis using an N-->S acyl shift.

Abstract:

: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.

journal_name

Biopolymers

journal_title

Biopolymers

authors

Ackrill T,Anderson DW,Macmillan D

doi

10.1002/bip.21473

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

495-503

issue

4

eissn

0006-3525

issn

1097-0282

journal_volume

94

pub_type

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