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Modulating protein-protein interactions by cyclic and macro-cyclic peptides. Prominent strategies and examples

AuthorsGonzález-Muñiz, Rosario CSIC ORCID; Bonache de Marcos, María Ángeles CSIC ORCID ; Pérez de Vega, M. Jesús
Keywordscyclic peptides
macrocyclic peptides
protein–protein interactions
computational design
biochemical methodologies
synthetic strategies
cell penetrating conjugates
Issue Date2021
PublisherMolecular Diversity Preservation International
CitationMolecules 26: 445-464 (2021)
AbstractCyclic and macrocyclic peptides constitute advanced molecules for modulating protein–protein interactions (PPIs). Although still peptide derivatives, they are metabolically more stable than linear counterparts, and should have a lower degree of flexibility, with more defined secondary structure conformations that can be adapted to imitate protein interfaces. In this review, we analyze recent progress on the main methods to access cyclic/macrocyclic peptide derivatives, with emphasis in a few selected examples designed to interfere within PPIs. These types of peptides can be from natural origin, or prepared by biochemical or synthetic methodologies, and their design could be aided by computational approaches. Some advances to facilitate the permeability of these quite big molecules by conjugation with cell penetrating peptides, and the incorporation of β-amino acid and peptoid structures to improve metabolic stability, are also commented. It is predicted that this field of research could have an important future mission, running in parallel to the discovery of new, relevant PPIs involved in pathological processes
Publisher version (URL)http://dx.doi.org/10.3390/molecules26020445
Identifiersdoi: 10.3390/molecules26020445
issn: 1420-3049
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