A trisbenzimidazole phosphoramidite building block enables high-yielding syntheses of rna-cleaving oligonucleotide conjugates

  • The RNA cleaving catalyst tris(2-aminobenzimidazole) when attached to the 5’ terminus of oligonucleotides cuts complementary RNA strands in a highly site-specific manner. Conjugation was previously achieved by the acylation of an amino linker by an active ester of the catalyst. However, this procedure was low yielding and not reliable. Here, a phosphoramidite building block is described that can be coupled to oligonucleotides by manual solid phase synthesis in total yields around 85%. Based on this chemistry, we have now studied the impact of LNA (locked nucleic acids) nucleotides on the rates and the site-specificities of RNA cleaving conjugates. The highest reaction rates and the most precise cuts can be expected when the catalyst is attached to a strong 5’ closing base pair and when the oligonucleotide contains several LNA units that are equally distributed in the strand. However, when placed in the 5’ position, LNA building blocks tend to diminish the specificity of RNA cleavage.

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Author:Felix Zellmann, Michael GöbelORCiDGND
Parent Title (German):Molecules
Place of publication:Basel
Document Type:Article
Date of Publication (online):2020/04/16
Date of first Publication:2020/04/16
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/05/04
Tag:2-aminobenzimidazole; DNA-LNA mixmers; artificial ribonuclease; guanidine analogs
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Open-Access-Publikationsfonds:Biochemie, Chemie und Pharmazie
Licence (German):License LogoCreative Commons - Namensnennung 4.0