Tunable heteroaromatic nitriles for selective bioorthogonal click reaction with cysteine

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

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.

• Jezik: Angleški jezik
• Ključne besede: labeling, monomers, nitrogen compounds, peptides, reactivity, proteins
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2023
• Št. strani: Str. 1271–1281
• Številčenje: Vol. 34, iss. 7
• PID: 20.500.12556/RUL-148256
• UDK: 615.4:54
• ISSN pri članku: 1043-1802
• DOI: 10.1021/acs.bioconjchem.3c00163
• COBISS.SI-ID: 156888323
• Datum objave v RUL: 07.08.2023

Gradivo je del revije

• Naslov: Bioconjugate chemistry
• Skrajšan naslov: Bioconjug. chem.
• Založnik: American Chemical Society
• ISSN: 1043-1802
• COBISS.SI-ID: 1492303

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: označevanje, monomeri, dušikove spojine, peptidi, proteini, reaktivnost, farmacevtska kemija

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0208
• Naslov: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Program financ.: Young Researchers