RNA hydrolysis by heterocyclic amidines and guanidines: parameters affecting reactivity

  • 2-Aminobenzimidazole 10, although a weak catalyst in the monomeric state, is a successful building block for effective artificial ribonucleases. In an effort to identify new building blocks with improved catalytic potential, RNA cleavage by a variety of heterocyclic amidines and guanidines has been studied. In addition to pKa values and steric effects, the energy difference between tautomeric forms seems to be another important parameter for catalysis. This information is available from quantum chemical calculations on higher levels, but semiempirical methods are sufficient to get a first estimate. According to this assumption, imidazoimidazol 18, characterized by isoenergetic tautomeric forms, is superior to 2-aminoimidazol 6, the best candidate among the simple compounds. By far the largest effects are seen with 2-aminoperimidine 24, which rapidly cleaves RNA even in the micromolar concentration range. The impressive reactivity, however, is related to a tendency of compound 24 to form polycationic aggregates which are the actual catalysts.
Author:Friederike DannebergGND, Hauke Westemeier, Philip Horx, Felix Zellmann, Kathrin DörrGND, Elisabeth Kalden, Mirco ZeigerGND, Abdullah Akpinar, Robert Berger, Michael GöbelORCiDGND
Parent Title (English):European journal of organic chemistry
Publisher:Wiley VCZ
Place of publication:Weinheim
Document Type:Article
Date of Publication (online):2021/09/16
Date of first Publication:2021/09/16
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/01/18
Tag:Ab initio calculations; Catalysis; Post-Hartree-Fock methods; RNA cleavage; Semi-empiricalcalculations
Issue:46 = Special Issue: In Memory of Klaus Hafner
Page Number:9
First Page:6358
Last Page:6366
Open Access funding enabled and organized by Projekt DEAL.
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung 4.0