@article {49686,
	title = {Peptide-triazolobenzodiazepine hybrids: a catalyst-free on-resin strategy to build complex therapeutic motifs into peptides},
	journal = {Chemistry-A European Journal},
	volume = {31},
	year = {2025},
	month = {JUN},
	type = {Article},
	abstract = {<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{\textquoteright}s adaptability for two site modifications in peptides involving both the N-terminus and Lys side chain amines. These modifications enhance the scope of {\textquoteleft}{\textquoteleft}peptide medicinal chemistry{\textquoteright}{\textquoteright} by creating multifunctional peptides with potential therapeutic applications. The method{\textquoteright}s compatibility with SPPS, room temperature conditions, and elimination of metal catalysis make it an efficient and powerful tool for peptide modification.</p>
},
	keywords = {hybrid peptides, peptide chemistry, peptide modification, spps compatibility, triazolobenzodiazepines},
	issn = {0947-6539},
	doi = {10.1002/chem.202500836},
	author = {Kamble, Sandip Sushila Mohan and Bodake, Supriya Mahadev and Marelli, Udaya Kiran}
}
