Next Article in Journal
Multivalent Ions as Reactive Crosslinkers for Biopolymers—A Review
Previous Article in Journal
5-Oxo-hexahydroquinoline Derivatives and Their Tetrahydroquinoline Counterparts as Multidrug Resistance Reversal Agents
Open AccessArticle

A Trisbenzimidazole Phosphoramidite Building Block Enables High-Yielding Syntheses of RNA-Cleaving Oligonucleotide Conjugates

Institute of Organic Chemistry and Chemical Biology, Goethe University Frankfurt, Max-von-Laue-Str. 7, D-60438 Frankfurt am Main, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Harri Lönnberg and Roger Strömberg
Molecules 2020, 25(8), 1842; https://doi.org/10.3390/molecules25081842
Received: 19 March 2020 / Revised: 13 April 2020 / Accepted: 14 April 2020 / Published: 16 April 2020
(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugate II)
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. View Full-Text
Keywords: 2-aminobenzimidazole; artificial ribonuclease; DNA-LNA mixmers; guanidine analogs 2-aminobenzimidazole; artificial ribonuclease; DNA-LNA mixmers; guanidine analogs
Show Figures

Graphical abstract

MDPI and ACS Style

Zellmann, F.; Göbel, M.W. A Trisbenzimidazole Phosphoramidite Building Block Enables High-Yielding Syntheses of RNA-Cleaving Oligonucleotide Conjugates. Molecules 2020, 25, 1842.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop