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Methylene Analogues of Neopetrosiamide as Potential Antimetastatic Agents: Solid-Supported Syntheses Using Diamino Diacids for Pre-Stapling of Peptides with Multiple Disulfides

Authors :
Daniel B Engelhardt
Marco J. van Belkum
Albert Remus R. Rosana
Cameron Pascoe
John C. Vederas
Source :
Organic Letters. 23:9216-9220
Publication Year :
2021
Publisher :
American Chemical Society (ACS), 2021.

Abstract

Neopetrosiamide, a 28-residue peptide from Neopetrosia sp., contains three disulfide bonds and hinders mammalian tumor cell invasion. Proper connectivity of disulfide bonds is crucial for activity. Synthetic replacement of single disulfide bridges with methylene bridges gives active analogues. Pre-stapling of one ring enhances the correct formation of the remaining disulfides by reducing isomeric possibilities and possibly initiating the correct 3D fold. Cloning and expression of neopetrosiamide in E. coli affords access to the natural linear peptide.

Details

ISSN :
15237052 and 15237060
Volume :
23
Database :
OpenAIRE
Journal :
Organic Letters
Accession number :
edsair.doi.dedup.....1b20bcbf5eb3fb6a70c391f827d1e154