Synthesis of lucifensin by native chemical ligation and characteristics of its isomer having different disulfide bridge pattern. (12th June 2014)

• Record Type: Journal Article
• Authors: Stanchev, Stancho; Zawada, Zbigniew; Monincová, Lenka; Bednárová, Lucie; Slaninová, Jiřina; Fučík, Vladimír; Čeřovský, Václav
• Is Part Of: Journal of peptide science. Volume 20:Number 9(2014:Sep.)
• Page Start: 725
• Page End: 735
• Publication Date: 2014-06-12
• Subjects: Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.2663
• Languages: English
• ISSNs: 1075-2617

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The antimicrobial 40‐amino‐acid‐peptide lucifensin was synthesized by native chemical ligation (NCL) using <italic>N</italic>‐acylbenzimidazolinone (Nbz) as a linker group. NCL is a method in which a peptide bond between two discreet peptide chains is created. This method has been applied to the synthesis of long peptides and proteins when solid‐phase synthesis is imcompatible. Two models of ligation were developed: [15 + 25] Ala‐Cys and [19 + 21] His‐Cys. The [19 + 21] His‐Cys method gives lower yield because of the lower stability of 18‐peptide‐His‐Nbz‐CONH<sub>2</sub> peptide, as suggested by density functional theory calculation. Acetamidomethyl‐deprotection and subsequent oxidation of the ligated linear lucifensin gave a mixture of lucifensin isomers, which differed in the location of their disulfide bridges only. The dominant isomer showed unnatural pairing of cysteines [C1−6], [C3−5], and [C2−4], which limits its ability to form <italic>α</italic>‐helical structure. The activity of isomeric lucifensin toward <italic>Bacillus subtilis</italic>, <italic>Staphylococcus aureus</italic>, and <italic>Micrococcus luteus</italic> was lower than that of the natural lucifensin. The desired product native lucifensin was prepared from this isomer using a one‐pot reduction with dithiotreitol and subsequent air oxidation in slightly alkaline medium. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.</p> </abstract>