Issue 17, 2015

Application of the Ugi reaction with multiple amino acid-derived components: synthesis and conformational evaluation of piperazine-based minimalist peptidomimetics

Abstract

The concurrent employment of α-amino acid-derived chiral components such as aldehydes and α-isocyanoacetates, in a sequential Ugi reaction/cyclization two-step strategy, opens the door to the synthesis of three structurally distinct piperazine-based scaffolds, characterized by the presence of L-Ala and/or L-Phe-derived side chains and bearing appropriate functionalities to be easily applied in peptide chemistry. By means of computational studies, these scaffolds have been demonstrated to act as minimalist peptidomimetics, able to mimic a well defined range of peptide secondary structures and therefore potentially useful for the synthesis of small-molecule PPI modulators. Preliminary biological evaluation of two different resistant hepatocellular carcinoma cellular lines, for which differentiation versus resistance ability seem to be strongly correlated with well defined types of PPIs, has revealed a promising antiproliferative activity for selected compounds.

Graphical abstract: Application of the Ugi reaction with multiple amino acid-derived components: synthesis and conformational evaluation of piperazine-based minimalist peptidomimetics

Supplementary files

Article information

Article type
Paper
Submitted
02 Feb 2015
Accepted
19 Mar 2015
First published
19 Mar 2015
This article is Open Access
Creative Commons BY license

Org. Biomol. Chem., 2015,13, 4993-5005

Author version available

Application of the Ugi reaction with multiple amino acid-derived components: synthesis and conformational evaluation of piperazine-based minimalist peptidomimetics

M. Stucchi, S. Cairati, R. Cetin-Atalay, M. S. Christodoulou, G. Grazioso, G. Pescitelli, A. Silvani, D. C. Yildirim and G. Lesma, Org. Biomol. Chem., 2015, 13, 4993 DOI: 10.1039/C5OB00218D

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