A Thiolactone Strategy for Straightforward Synthesis of Disulfide‐Linked Side‐Chain‐to‐Tail Cyclic Peptides Featuring an N‐Terminal Modification Handle. (20th February 2018)

• Record Type: Journal Article
• Authors: Van Lysebetten, Dorien; Felissati, Stefania; Antonatou, Eirini; Carrette, Lieselot L. G.; Espeel, Pieter; Focquet, Evelien; Du Prez, Filip E.; Madder, Annemieke
• Is Part Of: Chembiochem. Volume 19:Number 6(2018)
• Page Start: 641
• Page End: 646
• Publication Date: 2018-02-20
• Subjects: cyclisation -- lactones -- peptides -- sulfur -- synthesis design; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201700323
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: 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. Abstract : Getting to grips with cyclisation : A strategy that makes use of a N‐terminal thiolactone building block to provide easy access to side‐chain‐to‐tail disulfide cyclised peptides is reported. Different primary amines, which are used to open up this building block, can modify peptides of different lengths and introduce lipotails or handles for postcyclisation modification.