Fast Amide Bond Cleavage Assisted by a Secondary Amino and a Carboxyl Group—A Model for yet Unknown Peptidases?
| Autor: | Serhii H. Kharchenko, Anthony J. Kirby, Igor V. Komarov, Viacheslav Stepanenko, Aleksandr Hovtvianitsa, Andrew D. Bond, Aleksandr Yu. Ishchenko |
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| Přispěvatelé: | V Komarov, Igor [0000-0002-7908-9145], D Bond, Andrew [0000-0002-1744-0489], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular Stereochemistry medicine.medical_treatment Pharmaceutical Science model compound Cleavage (embryo) intein Catalysis Article Analytical Chemistry lcsh:QD241-441 Hydrolysis chemistry.chemical_compound twisted amide lcsh:Organic chemistry Amide Drug Discovery medicine Peptide bond Physical and Theoretical Chemistry Amines Protease intramolecular catalysis Bicyclic molecule Chemistry Organic Chemistry protease Amides amide hydrolysis Chemistry (miscellaneous) Molecular Medicine Intein Peptide Hydrolases |
| Zdroj: | Molecules Volume 24 Issue 3 Molecules, Vol 24, Iss 3, p 572 (2019) |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules24030572 |
| Popis: | Unconstrained amides that undergo fast hydrolysis under mild conditions are valuable sources of information about how amide bonds may be activated in enzymatic transformations. We report a compound possessing an unconstrained amide bond surrounded by an amino and a carboxyl group, each mounted in close proximity on a bicyclic scaffold. Fast amide hydrolysis of this model compound was found to depend on the presence of both the amino and carboxyl functions, and to involve a proton transfer in the rate-limiting step. Possible mechanisms for the hydrolytic cleavage and their relevance to peptide bond cleavage catalyzed by natural enzymes are discussed. Experimental observations suggest that the most probable mechanisms of the model compound hydrolysis might include a twisted amide intermediate and a rate-determining proton transfer. |
| Databáze: | OpenAIRE |
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