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(α,α-dimethyl)glycyl (dmg) PNAs: achiral PNA analogs that form stronger hybrids with cDNA relative to isosequential RNA.

Gourishankar A, Ganesh KN - Artif DNA PNA XNA (2012 Jan-Mar)

Bottom Line: They show a higher binding to DNA relative to that with isosequential RNA.The results complement our previous work that had demonstrated that cyclohexanyl-PNAs favor binding with cRNA compared with cDNA and imply that the biophysical and structural properties of PNAs can be directed by introduction of the right rigidity in PNA backbone devoid of chirality.This approach of tweaking selectivity in binding of PNA constructs by installing gem-dimethyl substitution in PNA backbone can be extended to further fine-tuning by similar substitution in the aminoethyl segment as well either individually or in conjunction with present substitution.

View Article: PubMed Central - PubMed

Affiliation: Indian Institute of Science Education and Research, Division of Organic Chemistry, National Chemical Laboratory, Pune, India.

ABSTRACT
The design and facile synthesis of sterically constrained new analogs of PNA having gem-dimethyl substitutions on glycine (dmg-PNA-T) is presented. The PNA oligomers [aminoethyl dimethylglycyl (aedmg) and aminopropyl dimethylglycyl (apdmg)] synthesized from the monomers 6 and 12) effected remarkable stabilization of homothyminePNA(2):homoadenine DNA/RNA triplexes and mixed base sequence duplexes with target cDNA or RNA. They show a higher binding to DNA relative to that with isosequential RNA. This may be a structural consequence of the sterically rigid gem-dimethyl group, imposing a pre-organized conformation favorable for complex formation with cDNA. The results complement our previous work that had demonstrated that cyclohexanyl-PNAs favor binding with cRNA compared with cDNA and imply that the biophysical and structural properties of PNAs can be directed by introduction of the right rigidity in PNA backbone devoid of chirality. This approach of tweaking selectivity in binding of PNA constructs by installing gem-dimethyl substitution in PNA backbone can be extended to further fine-tuning by similar substitution in the aminoethyl segment as well either individually or in conjunction with present substitution.

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General structures of PNA and DNA: B, nucleobase (T/A/C/G).
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Figure 1: General structures of PNA and DNA: B, nucleobase (T/A/C/G).

Mentions: Peptide nucleic acid (PNA) is an interesting class of nucleic acid mimics first reported by Nielsen and Buchardt1 that is formally neither a peptide nor a nucleic acid, but embodies the hybrid structural features of both classes of bio-molecules. The structure of PNA consists of repeating units of 2-aminoethylglycine (aeg) to which the nucleobases (A, C, T and G) are attached via a tertiary amide linkage (Fig. 1). PNA hybridizes to cDNA and RNA sequences with almost equal avidity in a sequence specific manner.2,3 This feature, combined with its biological and chemical stability, promised potential applications for in vitro diagnostics and antisense therapeutics.4-7 PNA directed against genomic DNA around the transcription start site effectively knocks down the expression of the targeted gene and is an effective addition to the arsenal of gene silencing agents.8,9


(α,α-dimethyl)glycyl (dmg) PNAs: achiral PNA analogs that form stronger hybrids with cDNA relative to isosequential RNA.

Gourishankar A, Ganesh KN - Artif DNA PNA XNA (2012 Jan-Mar)

General structures of PNA and DNA: B, nucleobase (T/A/C/G).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368815&req=5

Figure 1: General structures of PNA and DNA: B, nucleobase (T/A/C/G).
Mentions: Peptide nucleic acid (PNA) is an interesting class of nucleic acid mimics first reported by Nielsen and Buchardt1 that is formally neither a peptide nor a nucleic acid, but embodies the hybrid structural features of both classes of bio-molecules. The structure of PNA consists of repeating units of 2-aminoethylglycine (aeg) to which the nucleobases (A, C, T and G) are attached via a tertiary amide linkage (Fig. 1). PNA hybridizes to cDNA and RNA sequences with almost equal avidity in a sequence specific manner.2,3 This feature, combined with its biological and chemical stability, promised potential applications for in vitro diagnostics and antisense therapeutics.4-7 PNA directed against genomic DNA around the transcription start site effectively knocks down the expression of the targeted gene and is an effective addition to the arsenal of gene silencing agents.8,9

Bottom Line: They show a higher binding to DNA relative to that with isosequential RNA.The results complement our previous work that had demonstrated that cyclohexanyl-PNAs favor binding with cRNA compared with cDNA and imply that the biophysical and structural properties of PNAs can be directed by introduction of the right rigidity in PNA backbone devoid of chirality.This approach of tweaking selectivity in binding of PNA constructs by installing gem-dimethyl substitution in PNA backbone can be extended to further fine-tuning by similar substitution in the aminoethyl segment as well either individually or in conjunction with present substitution.

View Article: PubMed Central - PubMed

Affiliation: Indian Institute of Science Education and Research, Division of Organic Chemistry, National Chemical Laboratory, Pune, India.

ABSTRACT
The design and facile synthesis of sterically constrained new analogs of PNA having gem-dimethyl substitutions on glycine (dmg-PNA-T) is presented. The PNA oligomers [aminoethyl dimethylglycyl (aedmg) and aminopropyl dimethylglycyl (apdmg)] synthesized from the monomers 6 and 12) effected remarkable stabilization of homothyminePNA(2):homoadenine DNA/RNA triplexes and mixed base sequence duplexes with target cDNA or RNA. They show a higher binding to DNA relative to that with isosequential RNA. This may be a structural consequence of the sterically rigid gem-dimethyl group, imposing a pre-organized conformation favorable for complex formation with cDNA. The results complement our previous work that had demonstrated that cyclohexanyl-PNAs favor binding with cRNA compared with cDNA and imply that the biophysical and structural properties of PNAs can be directed by introduction of the right rigidity in PNA backbone devoid of chirality. This approach of tweaking selectivity in binding of PNA constructs by installing gem-dimethyl substitution in PNA backbone can be extended to further fine-tuning by similar substitution in the aminoethyl segment as well either individually or in conjunction with present substitution.

Show MeSH
Related in: MedlinePlus