Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates As Gene Expression Control Compounds

Overview

Journal J Nucleic Acids

Publisher Wiley

Date 2023 Mar 24

PMID 36960406

Authors

Kazuo Kamaike

Mutsumi Sano

Daisuke Sakata

Yu Nishihara

Hiroaki Amino

Akihiro Ohtsuki

Yui Okada

Takafumi Miyakawa

Makoto Kogawara

Mai Tsutsumi

Misato Takahashi

Etsuko Kawashima

Koichiro Ota

Hiroaki Miyaoka

Affiliations

Soon will be listed here.

Abstract

MGB polyamide-oligonucleotide conjugates - with linked MGB polyamides at the 2-exocyclic amino group of a guanine base using aminoalkyl linkers were synthesized and evaluated in terms of binding affinity for complementary DNA containing the MGB polyamide binding sequence using and CD analyses. The MGB polyamides comprised pyrrole polyamides (Py- and Py-), which possess binding affinity for A-T base pairs, and imidazole (Im-) and pyrrole--imidazole (Py--Im-) polyamide hairpin motifs, which possess binding affinity for C-G base pairs. It was found that the stability of modified dsDNA was greatly influenced by the linker length. Py- and Py-oligonucleotide conjugates ( ( = 4) and ( = 4)) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA. Although Im-oligonucleotide conjugate ( = 4) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA, stabilization of dsDNA by the imidazole amide moiety of ( = 4) was lower compared with the pyrrole amide moiety of ( = 4). The Py--Im-oligonucleotide conjugate ( = 2), which possesses binding affinity for C-G base pairs via a pyrrole/imidazole combination and contains a 2-aminoethyl linker, showed high binding ability for complementary DNA. Furthermore, the DNA sequence recognition of MGB polyamide-oligonucleotide conjugates was investigated using single-base mismatch DNAs, which possess a mismatch base in the MGB polyamide binding sequence. The Py--Im-oligonucleotide conjugate ( = 2) showed high sequence recognition ability for complementary DNA.

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