02222nas a2200217   4500008004100000022001400041245012800055210006900183260000800252490000700260520141200267653002001679653002201699653002501721653002301746653002801769100003101797700002901828700002601857856012101883       2025                        eng d  a0947-653900aPeptide-triazolobenzodiazepine hybrids: a catalyst-free on-resin strategy to build complex therapeutic motifs into peptides0 aPeptidetriazolobenzodiazepine hybrids a catalystfree onresin str  cJUN0 v313 a<p>
	The merger of peptide and heterocyclic chemistry presents significant opportunities for enhancing the structural and functional diversity of therapeutic agents. In this study, we introduce a streamlined on-resin method to modify peptides at the N-terminus amines and the side chain amines of Lys/Orn amino acids by incorporating the biologically active triazolobenzodiazepine scaffold. In the presented solid-phase peptide synthesis (SPPS), the triazolobenzodiazepine core is formed on-resin through a combination of N-alkylation, amide bond formation, and an alkyne-azide 1,3-dipolar cycloaddition, of which the latter two happen as a single-step one-pot reaction- proceeding under mild conditions without metal catalysts. This protocol tolerates a wide variety of amino acids and functional groups, providing a versatile method for synthesizing peptide-triazolobenzodiazepine hybrids. Using orthogonal protection group strategies, we further demonstrate the method's adaptability for two site modifications in peptides involving both the N-terminus and Lys side chain amines. These modifications enhance the scope of ``peptide medicinal chemistry'' by creating multifunctional peptides with potential therapeutic applications. The method's compatibility with SPPS, room temperature conditions, and elimination of metal catalysis make it an efficient and powerful tool for peptide modification.</p>
10ahybrid peptides10apeptide chemistry10apeptide modification10aspps compatibility10atriazolobenzodiazepines1 aKamble, Sandip, Sushila Mo1 aBodake, Supriya, Mahadev1 aMarelli, Udaya, Kiran  uhttps://library.ncl.res.in/content/peptide-triazolobenzodiazepine-hybrids-catalyst-free-resin-strategy-build-complex