The effects of unnatural base pairs and mispairs on DNA duplex stability and solvation

In an effort to develop unnatural DNA base pairs we examined six pyridine-based nucleotides, d3MPy, d4MPy, d5MPy, d34DMPy, d35DMPy and d45DMPy. Each bears a pyridyl nucleobase scaffold but they are differentiated by methyl substitution, and were designed to vary both inter- and intra-strand packing...

Full description

Bibliographic Details
Main Authors:	Hwang, Gil Tae, Hari, Yoshiyuki, Romesberg, Floyd E.
Format:	Online
Language:	English
Published:	Oxford University Press 2009
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724283/

id	pubmed-2724283
recordtype	oai_dc
spelling	pubmed-27242832009-08-18 The effects of unnatural base pairs and mispairs on DNA duplex stability and solvation Hwang, Gil Tae Hari, Yoshiyuki Romesberg, Floyd E. Chemistry and Synthetic Biology In an effort to develop unnatural DNA base pairs we examined six pyridine-based nucleotides, d3MPy, d4MPy, d5MPy, d34DMPy, d35DMPy and d45DMPy. Each bears a pyridyl nucleobase scaffold but they are differentiated by methyl substitution, and were designed to vary both inter- and intra-strand packing within duplex DNA. The effects of the unnatural base pairs on duplex stability demonstrate that the pyridine scaffold may be optimized for stable and selective pairing, and identify one self pair, the pair formed between two d34DMPy nucleotides, which is virtually as stable as a dA:dT base pair in the same sequence context. In addition, we found that the incorporation of either the d34DMPy self pair or a single d34DMPy paired opposite a natural dA significantly increases oligonucleotide hybridization fidelity at other positions within the duplex. Hypersensitization of the duplex to mispairing appears to result from global and interdependent solvation effects mediated by the unnatural nucleotide(s) and the mispair. The results have important implications for our efforts to develop unnatural base pairs and suggest that the unnatural nucleotides might be developed as novel biotechnological tools, diagnostics, or therapeutics for applications where hybridization stringency is important. Oxford University Press 2009-08 2009-06-10 /pmc/articles/PMC2724283/ /pubmed/19515938 http://dx.doi.org/10.1093/nar/gkp467 Text en © 2009 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Hwang, Gil Tae Hari, Yoshiyuki Romesberg, Floyd E.
spellingShingle	Hwang, Gil Tae Hari, Yoshiyuki Romesberg, Floyd E. The effects of unnatural base pairs and mispairs on DNA duplex stability and solvation
author_facet	Hwang, Gil Tae Hari, Yoshiyuki Romesberg, Floyd E.
author_sort	Hwang, Gil Tae
title	The effects of unnatural base pairs and mispairs on DNA duplex stability and solvation
title_short	The effects of unnatural base pairs and mispairs on DNA duplex stability and solvation
title_full	The effects of unnatural base pairs and mispairs on DNA duplex stability and solvation
title_fullStr	The effects of unnatural base pairs and mispairs on DNA duplex stability and solvation
title_full_unstemmed	The effects of unnatural base pairs and mispairs on DNA duplex stability and solvation
title_sort	effects of unnatural base pairs and mispairs on dna duplex stability and solvation
description	In an effort to develop unnatural DNA base pairs we examined six pyridine-based nucleotides, d3MPy, d4MPy, d5MPy, d34DMPy, d35DMPy and d45DMPy. Each bears a pyridyl nucleobase scaffold but they are differentiated by methyl substitution, and were designed to vary both inter- and intra-strand packing within duplex DNA. The effects of the unnatural base pairs on duplex stability demonstrate that the pyridine scaffold may be optimized for stable and selective pairing, and identify one self pair, the pair formed between two d34DMPy nucleotides, which is virtually as stable as a dA:dT base pair in the same sequence context. In addition, we found that the incorporation of either the d34DMPy self pair or a single d34DMPy paired opposite a natural dA significantly increases oligonucleotide hybridization fidelity at other positions within the duplex. Hypersensitization of the duplex to mispairing appears to result from global and interdependent solvation effects mediated by the unnatural nucleotide(s) and the mispair. The results have important implications for our efforts to develop unnatural base pairs and suggest that the unnatural nucleotides might be developed as novel biotechnological tools, diagnostics, or therapeutics for applications where hybridization stringency is important.
publisher	Oxford University Press
publishDate	2009
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724283/
_version_	1611441289075621888

The effects of unnatural base pairs and mispairs on DNA duplex stability and solvation

Similar Items