Selectivity Modulation and Structure of alpha/aza-beta(3) Cyclic Antimicrobial Peptides

Mathieu Laurencin 1 Matthieu Simon 1, 2 Yannick Fleury 3 Michele Baudy-Floc'H 1 Arnaud Bondon 1 Baptiste Legrand 2, 1
1 ISCR - Institut des Sciences Chimiques de Rennes
2 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
3 IUEM - Institut Universitaire Européen de la Mer
Abstract : Potent and selective antimicrobial cyclic pseudopeptides (ACPPs) mixing α- and aza-β -amino acids were developed. Cyclopseudopeptide sequences were designed to investigate the impact of some intrinsic molecular parameters on their biological activities. Fine changes in the nature of the side chains strongly modulated the selectivity of the ACPPs with regard to hemolysis versus antimicrobial activity. The conformational preference of such compounds in various media was extensively studied, and the typical structure of cyclic α/aza-β -pseudopeptides is described for the first time. Interestingly, such scaffolds are stabilized by successive inverse γ- and N-N turns (hydrazino turns), a unique feature due to the aza-β residues. The α-amino acid side chains form a cluster on one face of the ring, while the aza-β -amino acid side chains are projected around the ring in the equatorial orientation. Such structural data are particularly valuable to fine-tune the bioactivity of these ACPPs by a structure-based approach.
Keywords : peptidomimetics peptides cyclic peptides aza amino acids antibiotics
Document type :
Journal articles
Complete list of metadatas

Cited literature [68 references]  Display  Hide  Download
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01807077
Contributor : Laurent Jonchère <>
Submitted on : Tuesday, June 19, 2018 - 10:11:23 AM
Last modification on : Wednesday, October 2, 2019 - 1:36:20 PM
Long-term archiving on : Tuesday, September 25, 2018 - 12:22:12 AM

File

Legrand et al_Selectivity Modu...
Files produced by the author(s)

Identifiers

Collections

UNIV-RENNES1 | ISCR | INC-CNRS | CHIMIE | UNIV-MONTPELLIER | UNIV-RENNES | ISCR-CORINT | INSA-RENNES | UNIV-BREST | UR1-UFR-SPM | IRD | INSA-GROUPE

Citation

Mathieu Laurencin, Matthieu Simon, Yannick Fleury, Michele Baudy-Floc'H, Arnaud Bondon, et al.. Selectivity Modulation and Structure of alpha/aza-beta(3) Cyclic Antimicrobial Peptides. Chemistry - A European Journal, Wiley-VCH Verlag, 2018, 24 (23), pp.6191-6201. ⟨10.1002/chem.201800152⟩. ⟨hal-01807077⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

131

Files downloads

93