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

Date
2015
Authors
Stucchi, M.
Cairati, S.
Cetin-Atalay, R.
Christodoulou, M.S.
Grazioso G.
Pescitelli G.
Silvani, A.
Yildirim, D.C.
Lesma G.
Advisor
Instructor
Source Title
Organic and Biomolecular Chemistry
Print ISSN
14770520
Electronic ISSN
Publisher
Royal Society of Chemistry
Volume
13
Issue
17
Pages
4993 - 5005
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
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. © The Royal Society of Chemistry 2015.

Course
Other identifiers
Book Title
Keywords
Amino acids, Chemical reactions, Mobile security, Peptides, Stereochemistry, Alpha-amino acids, Anti-proliferative activities, Biological evaluation, Computational studies, Hepatocellular carcinoma, Peptide chemistries, Peptide secondary structures, Small molecules, Synthesis (chemical), alanine, peptidomimetic agent, phenylalanine, piperazine, piperazine derivative, cell differentiation, cell proliferation, chemistry, conformation, cyclization, dose response, drug effects, human, quantum theory, structure activity relation, synthesis, tumor cell line, Alanine, Cell Differentiation, Cell Line, Tumor, Cell Proliferation, Cyclization, Dose-Response Relationship, Drug, Humans, Molecular Conformation, Peptidomimetics, Phenylalanine, Piperazines, Quantum Theory, Structure-Activity Relationship
Citation
Published Version (Please cite this version)