Matic Proj (Author), Nika Strašek (Author), Stane Pajk (Author), Damijan Knez (Author), Izidor Sosič (Author)

Abstract

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.

Keywords

označevanje;monomeri;dušikove spojine;peptidi;proteini;reaktivnost;labeling;monomers;nitrogen compounds;peptides;reactivity;proteins;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FFA - Faculty of Pharmacy
UDC: 615.4:54
COBISS: 156888323 Link will open in a new window
ISSN: 1043-1802
Views: 228
Downloads: 32
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Other data

Secondary language: Slovenian
Secondary keywords: Peptidi;Farmacevtska kemija;Proteini;
Type (COBISS): Article
Pages: str. 1271-1281
Volume: ǂVol. ǂ34
Issue: ǂno. ǂ7
Chronology: 2023
DOI: 10.1021/acs.bioconjchem.3c00163
ID: 19747909