20.500.12556/RUL-148256 Tunable heteroaromatic nitriles for selective bioorthogonal click reaction with cysteine The binucleophilic properties of 1,2-aminothiol and its rare occurrence in nature make it a useful reporter for tracking molecules in living systems. The 1,2-aminothiol moiety is present in cysteine, which is a substrate for a biocompatible click reaction with heteroaromatic nitriles. Despite the wide range of applications for this reaction, the scope of nitrile substrates has been explored only to a limited extent. In this study, we expand the chemical space of heteroaromatic nitriles for bioconjugation under physiologically relevant conditions. We systematically assembled a library of 116 2-cyanobenzimidazoles, 1-methyl-2-cyanobenzimidazoles, 2-cyanobenzothiazoles, and 2-cyanobenzoxazoles containing electron-donating and electron-withdrawing substituents at all positions of the benzene ring. The compounds were evaluated for their stability, reactivity, and selectivity toward the N-terminal cysteine of model oligopeptides. In comparison to the benchmark 6-hydroxy-2-cyanobenzothiazole or 6-amino-2-cyanobenzothiazole, we provide highly selective and moderately reactive nitriles as well as highly reactive yet less selective analogs with a variety of enabling attachment chemistries to aid future applications in bioconjugation, chemical biology, and nanomaterial science. labeling monomers nitrogen compounds peptides reactivity proteins označevanje monomeri dušikove spojine peptidi proteini reaktivnost farmacevtska kemija true false true Angleški jezik Slovenski jezik Članek v reviji 2023-08-07 14:02:14 2023-08-07 14:02:26 2023-11-16 11:55:07 0000-00-00 00:00:00 2023 0 0 Str. 1271–1281 iss. 7 Vol. 34 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4:54 1043-1802 10.1021/acs.bioconjchem.3c00163 156888323 acs.bioconjchem.3c00163.pdf acs.bioconjchem.3c00163.pdf 1 CD5A9CA4DC87913C3A85B512A3F239ED e03182eff9502883f252c16cb0606cc6035b395ba2f1d157dab8db987b4f22e0 737a91f7-351a-11ee-aeaf-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=172317 https://pubs.acs.org/doi/10.1021/acs.bioconjchem.3c00163 1 430bfaea-351a-11ee-aeaf-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=172316 Fakulteta za farmacijo 0 0 0