Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 4, 2014
Previous Article Next Article

Convergent diversity-oriented side-chain macrocyclization scan for unprotected polypeptides

Author affiliations

Abstract

Here we describe a general synthetic platform for side-chain macrocyclization of an unprotected peptide library based on the SNAr reaction between cysteine thiolates and a new generation of highly reactive perfluoroaromatic small molecule linkers. This strategy enabled us to simultaneously “scan” two cysteine residues positioned from i, i + 1 to i, i + 14 sites in a polypeptide, producing 98 macrocyclic products from reactions of 14 peptides with 7 linkers. A complementary reverse strategy was developed; cysteine residues within the polypeptide were first modified with non-bridging perfluoroaryl moieties and then commercially available dithiol linkers were used for macrocyclization. The highly convergent, site-independent, and modular nature of these two strategies coupled with the unique chemoselectivity of a SNAr transformation allows for the rapid diversity-oriented synthesis of hybrid macrocyclic peptide libraries with varied chemical and structural complexities.

Graphical abstract: Convergent diversity-oriented side-chain macrocyclization scan for unprotected polypeptides

Back to tab navigation

Supplementary files

Article information


Submitted
01 Nov 2013
Accepted
19 Nov 2013
First published
06 Dec 2013

Org. Biomol. Chem., 2014,12, 566-573
Article type
Paper

Convergent diversity-oriented side-chain macrocyclization scan for unprotected polypeptides

Y. Zou, A. M. Spokoyny, C. Zhang, M. D. Simon, H. Yu, Y. Lin and B. L. Pentelute, Org. Biomol. Chem., 2014, 12, 566
DOI: 10.1039/C3OB42168F

Social activity

Search articles by author

Spotlight

Advertisements