Jul 2026· Organic and biomolecular chemistry· Vol 24, pp. 6992 - 6998· 0 citations
Medicine
Abstract
Mediation of protein–protein interactions with molecules that bind strongly and selectively to one of the partners at the protein interface is a promising therapeutic strategy for myriad diseases. One such approach is the rational design of non-peptidic scaffolds that reproduce the display of amino acid side chains from one face of a secondary structural element. We have previously disclosed proof-of principle syntheses of β-strand mimetics composed of alternating (hetero)aromatic and cyclic urea units, conformationally preorganised through dipolar repulsion in organic solvents, that are in good agreement with the i, i + 2, and i + 4 side-chain vectors of a canonical strand. Here we demonstrate sequence diversity of the approach through the incorporation of hydrophobic and hydrophilic side-chain mimics via an improved synthetic route. The scaffold is conformationally preorganised for target binding in aqueous media including buffer, is readily soluble, and thus is suitable for elaboration and deployment against specific protein targets.
G-quadruplexes (G4s) are noncanonical nucleic acid structures involved in the regulation of key biological processes and represent attractive targets for therapeutic intervention. In this study, we report the design, synthesis, and biophysical evaluation of a new family of water-soluble heptacyclic oligo-heteroaryl lig...
Giorgia Fracchioni, A. M. Caramiello, M. Nadai et al.· ACS Omega· 0 citations
Peptide-based materials have enormous potential for applications including therapeutics, sensing, catalysis, and flexible electronics. Recent material discovery screenings through peptide sequence space have identified a class of amphiphilic heme-containing peptides that self-assemble at the nanoscale while efficient...
Jesse L. Prelesnik, A. P. Lau, Nathan C. Laud et al.· Journal of the American Chem...· 0 citations
The results demonstrate that a conformational rigidification through a bridged scaffold, implemented while preserving membrane permeability, is a highly effective strategy for achieving isoform selectivity.
M. Kage, Hatsuo Kawada, Koji Takano et al.· Journal of the American Chem...· 0 citations
This study reports for the first time that peptoid hexamers can adopt a unique looplike structure with a cis-cis-trans-cis-cis-cis arrangement of the backbone amides, and reveals a distinct circular dichroism (CD) fingerprint for loop-shaped peptoids containing chiral aromatic Nspe monomers.
Zacharie Bordas, Baptiste Legrand, Souleymane Sarr et al.· Journal of the American Chem...· 0 citations
This review comprehensively examines the biological significance of PPIs in human disease and details how MPPs effectively modulate historically undruggable targets, highlighting current synthetic strategies, peptide engineering platforms, and the clinical and preclinical status of leading MPP candidates, while weighin...
Peptide stapling exerts profound effects on key peptide properties, including metabolic stability, cell membrane permeability, and conformational constraint. Herein, we report a mild and efficient 2,4-dichloro-1,3,5-triazine-mediated stapling strategy for the selective cross-linking of lysine side-chain amines. This ap...
