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Construction of challenging proline–proline junctions via diselenide–selenoester ligation chemistry

Sayers, Jessica; Karpati, Phillip M. T.; Mitchell, Nicholas J.; Goldys, Anna M.; Kwong, Stephen M.; Firth, Neville; Chan, Bun; Payne, Richard J.


Jessica Sayers

Phillip M. T. Karpati

Anna M. Goldys

Stephen M. Kwong

Neville Firth

Bun Chan

Richard J. Payne


Polyproline sequences are highly abundant in prokaryotic 10 and eukaryotic proteins, where they serve as key components of 11 secondary structure. To date, construction of the proline?proline motif 12 has not been possible owing to steric congestion at the ligation junction, 13 together with an n ? ?* electronic interaction that reduces the 14 reactivity of acylated proline residues at the C-terminus of peptides. 15 Here, we harness the enhanced reactivity of prolyl selenoesters and a 16 trans-?-selenoproline moiety to access the elusive proline?proline 17 junction for the ?rst time through a diselenide?selenoester ligation? 18 deselenization manifold. The e?cient nature of this chemistry is 19 highlighted in the high-yielding one-pot assembly of two proline-rich 20 polypeptide targets, submaxillary gland androgen regulated protein 3B 21 and lumbricin-1. This method provides access to the most challenging of ligation junctions, thus enabling the construction of 22 previously intractable peptide and protein targets of increasing structural complexity.


Sayers, J., Karpati, P. M. T., Mitchell, N. J., Goldys, A. M., Kwong, S. M., Firth, N., …Payne, R. J. (2018). Construction of challenging proline–proline junctions via diselenide–selenoester ligation chemistry. Journal of the American Chemical Society, 140(41), 13327-13334.

Journal Article Type Article
Acceptance Date Sep 21, 2018
Online Publication Date Sep 21, 2018
Publication Date Oct 17, 2018
Deposit Date Oct 23, 2018
Publicly Available Date Sep 22, 2019
Journal Journal of the American Chemical Society
Print ISSN 0002-7863
Electronic ISSN 1520-5126
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 140
Issue 41
Pages 13327-13334
Keywords Colloid and Surface Chemistry; Biochemistry; General Chemistry; Catalysis
Public URL
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