Cargando…

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

MGB polyamide-oligonucleotide conjugates ON 1-4 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 T(m) and CD analy...

Descripción completa

Detalles Bibliográficos
Autores principales: Kamaike, Kazuo, Sano, Mutsumi, Sakata, Daisuke, Nishihara, Yu, Amino, Hiroaki, Ohtsuki, Akihiro, Okada, Yui, Miyakawa, Takafumi, Kogawara, Makoto, Tsutsumi, Mai, Takahashi, Misato, Kawashima, Etsuko, Ota, Koichiro, Miyaoka, Hiroaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030224/
https://www.ncbi.nlm.nih.gov/pubmed/36960406
http://dx.doi.org/10.1155/2023/2447998
_version_ 1784910309558845440
author Kamaike, Kazuo
Sano, Mutsumi
Sakata, Daisuke
Nishihara, Yu
Amino, Hiroaki
Ohtsuki, Akihiro
Okada, Yui
Miyakawa, Takafumi
Kogawara, Makoto
Tsutsumi, Mai
Takahashi, Misato
Kawashima, Etsuko
Ota, Koichiro
Miyaoka, Hiroaki
author_facet Kamaike, Kazuo
Sano, Mutsumi
Sakata, Daisuke
Nishihara, Yu
Amino, Hiroaki
Ohtsuki, Akihiro
Okada, Yui
Miyakawa, Takafumi
Kogawara, Makoto
Tsutsumi, Mai
Takahashi, Misato
Kawashima, Etsuko
Ota, Koichiro
Miyaoka, Hiroaki
author_sort Kamaike, Kazuo
collection PubMed
description MGB polyamide-oligonucleotide conjugates ON 1-4 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 T(m) and CD analyses. The MGB polyamides comprised pyrrole polyamides (Py(4)- and Py(3)-), which possess binding affinity for A-T base pairs, and imidazole (Im(3)-) and pyrrole-γ-imidazole (Py(3)-γ-Im(3)-) 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(4)- and Py(3)-oligonucleotide conjugates (ON 1 (n = 4) and ON 2 (n = 4)) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA. Although Im(3)-oligonucleotide conjugate ON 3 (n = 4) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA, stabilization of dsDNA by the imidazole amide moiety of ON 3 (n = 4) was lower compared with the pyrrole amide moiety of ON 2 (n = 4). The Py(3)-γ-Im(3)-oligonucleotide conjugate ON 4 (n = 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(3)-γ-Im(3)-oligonucleotide conjugate ON 4 (n = 2) showed high sequence recognition ability for complementary DNA.
format Online
Article
Text
id pubmed-10030224
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-100302242023-03-22 Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates as Gene Expression Control Compounds Kamaike, Kazuo Sano, Mutsumi Sakata, Daisuke Nishihara, Yu Amino, Hiroaki Ohtsuki, Akihiro Okada, Yui Miyakawa, Takafumi Kogawara, Makoto Tsutsumi, Mai Takahashi, Misato Kawashima, Etsuko Ota, Koichiro Miyaoka, Hiroaki J Nucleic Acids Research Article MGB polyamide-oligonucleotide conjugates ON 1-4 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 T(m) and CD analyses. The MGB polyamides comprised pyrrole polyamides (Py(4)- and Py(3)-), which possess binding affinity for A-T base pairs, and imidazole (Im(3)-) and pyrrole-γ-imidazole (Py(3)-γ-Im(3)-) 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(4)- and Py(3)-oligonucleotide conjugates (ON 1 (n = 4) and ON 2 (n = 4)) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA. Although Im(3)-oligonucleotide conjugate ON 3 (n = 4) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA, stabilization of dsDNA by the imidazole amide moiety of ON 3 (n = 4) was lower compared with the pyrrole amide moiety of ON 2 (n = 4). The Py(3)-γ-Im(3)-oligonucleotide conjugate ON 4 (n = 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(3)-γ-Im(3)-oligonucleotide conjugate ON 4 (n = 2) showed high sequence recognition ability for complementary DNA. Hindawi 2023-03-14 /pmc/articles/PMC10030224/ /pubmed/36960406 http://dx.doi.org/10.1155/2023/2447998 Text en Copyright © 2023 Kazuo Kamaike et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kamaike, Kazuo
Sano, Mutsumi
Sakata, Daisuke
Nishihara, Yu
Amino, Hiroaki
Ohtsuki, Akihiro
Okada, Yui
Miyakawa, Takafumi
Kogawara, Makoto
Tsutsumi, Mai
Takahashi, Misato
Kawashima, Etsuko
Ota, Koichiro
Miyaoka, Hiroaki
Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates as Gene Expression Control Compounds
title Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates as Gene Expression Control Compounds
title_full Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates as Gene Expression Control Compounds
title_fullStr Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates as Gene Expression Control Compounds
title_full_unstemmed Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates as Gene Expression Control Compounds
title_short Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates as Gene Expression Control Compounds
title_sort synthesis and evaluation of mgb polyamide-oligonucleotide conjugates as gene expression control compounds
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030224/
https://www.ncbi.nlm.nih.gov/pubmed/36960406
http://dx.doi.org/10.1155/2023/2447998
work_keys_str_mv AT kamaikekazuo synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds
AT sanomutsumi synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds
AT sakatadaisuke synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds
AT nishiharayu synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds
AT aminohiroaki synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds
AT ohtsukiakihiro synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds
AT okadayui synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds
AT miyakawatakafumi synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds
AT kogawaramakoto synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds
AT tsutsumimai synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds
AT takahashimisato synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds
AT kawashimaetsuko synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds
AT otakoichiro synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds
AT miyaokahiroaki synthesisandevaluationofmgbpolyamideoligonucleotideconjugatesasgeneexpressioncontrolcompounds