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A Thiolactone Strategy for Straightforward Synthesis of Disulfide‐Linked Side‐Chain‐to‐Tail Cyclic Peptides Featuring an N‐Terminal Modification Handle
Author(s) -
Van Lysebetten Dorien,
Felissati Stefania,
Antonatou Eirini,
Carrette Lieselot L. G.,
Espeel Pieter,
Focquet Evelien,
Du Prez Filip E.,
Madder Annemieke
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700323
Subject(s) - thiolactone , peptide , chemistry , bifunctional , combinatorial chemistry , amine gas treating , disulfide bond , alkyl , chain (unit) , side chain , terminal (telecommunication) , stereochemistry , organic chemistry , biochemistry , computer science , polymer , catalysis , telecommunications , physics , astronomy
The development of straightforward and versatile peptide cyclisation methods is highly desired to meet the demand for more stable peptide‐based drugs. Herein, a new method for the synthesis of side‐chain‐to‐tail cyclic peptides with the simultaneous introduction of an N‐terminal handle, based on the introduction of an N‐terminal thiolactone building block, is described. A primary amine liberates a homocysteine analogue from the thiolactone building block, which further enables cyclisation of the peptide through disulfide‐bond formation with a C‐terminal cysteamine. Postcyclisation modification can be achieved by using small bifunctional amines. Alternatively, the synthesis of lipopeptides is demonstrated through direct thiolactone opening with long‐chain alkyl amines.