Synthetic strategies to prepare novel bioactive lysine and peptide conjugates with triazolium derivatives

Peptide conjugates with small molecules are increasingly used, particularly in pharmaceutical applications, and can be designed as carriers, stabilizing agents, or active ingredients per se. In many conjugates a drug-like molecule is responsible for the activity, but the efficacy can be enhanced by the peptide sequence, e.g. by providing an additional binding specificity. Research for new peptide- and peptidomimetic drug conjugates is leading to the development of novel compounds with anticancer and antimicrobial activity and for diagnostic applications. Dihydro-[1,2,4]triazolo [4,3-a]pyridine-2-ium carboxylates known as Safirinium dyes, have been previously investigated as antibacterial and imaging agents.1 Heterocyclic compounds, such as N-benzoylpyrazoles and N‐benzoylindazoles were found to be good inhibitors of human neutrophil elastase (HNE). To the best of our knowledge, Safirinium derivatives and conjugates were not tested as enzyme inhibitors. Making available a straightforward synthesis strategy to prepare lysine and peptide conjugates with Safirinium dyes is key to enable their exploitation for pharmaceutical and cosmeceutical applications, and as building blocks for the synthesis of novel bioactive peptides.