Construction of Challenging Proline–Proline Junctions via Diselenide–Selenoester Ligation Chemistry

• DOI: 10.1021/jacs.8b07877
• Publication Date: 2018-09-21T21:27:21Z
• Authors: Jessica Sayers; Phillip M. T. Kar...; Nicholas J. Mitchell; Anna M. Goldys; Stephen M. Kwong; Neville Firth; Bun Chan; Richard J. Payne
• Keywords: Polyproline helix; Diselenide

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