Flat Amino Acid Surrogates Induce Turn Conformers: Synthesis, Nitrogen Chirality, Conformation and Biomedical Applications of N-Amino Triazolone (Nat) Peptides
Year: 2026
Type: preprint
Abstract: 4-Amino-1,2,4-triazol-3-ones are relatively flat but shown to serve as turn inducing amino amide surrogates in peptides. Model N-amino triazolone (Nat) peptides were first synthesized and shown by NMR studies in solution to exhibit diastereotopic glycine methylene protons indicative of chiral nitrogen with inversion barriers around 17-18 kcal/mol, as well as solvent shielded amide protons indicative of involvement in intramolecular hydrogen bonds in -turn conformers. In crystal structures packing forces likely perturbed intramolecular hydrogen bonding, but Nat residues exhibited dihedral angles characteristic of the i+1 central position of certain -turn structures. Introduction of Nat residues as turn surrogates into antimicrobial and anti-inflammatory peptide analogs gave respectively comparable activity against Gram positive and negative microorganisms as well as potent ability to mitigate Toll receptor agonist effects on cytokine and chemokine levels by the modulation of the cluster-of-differentiation-36 receptor (CD36) in
Source: ChemRxiv
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Awards: G103969113, G1311762383, G2367382385, Regroupements stratégiques — Synthèse chimique et catalyse, Technologies propres, G3733136027, G3919604117, G4260133985, G472691115, G4894166530, G5205116276, G5620742401, Advances in Amino Acid Chemistry and Peptide Mimicry, G6078179141, G8093361439, G832689143
OpenAlex ID: W7211906488