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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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Figure 6. CD spectra of (A) aedmg-PNA2:DNA triplexes and (B) apdmg-PNA:DNA triplexes. The number shown above each curve refers to the PNA sequence shown in Table 1.
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Figure 6: Figure 6. CD spectra of (A) aedmg-PNA2:DNA triplexes and (B) apdmg-PNA:DNA triplexes. The number shown above each curve refers to the PNA sequence shown in Table 1.

Mentions: In order to examine if aedmg-PNAs have any significant differences in their overall conformational features, the CD spectra of PNA complexes with DNA were examined (Fig. 6). The PNA2:DNA triplexes exhibit two maxima at 260 nm and 280 nm, a minimum at 246 nm and crossover points around 250 nm. The double hump profile in the region 260–280 nm is characteristic of polyT-polyA:polyT (PNA2:DNA) triplexes.28 The CD profiles of dmg-PNA:DNA duplexes were similar to those of the control achiral aeg-PNA:DNA duplexes indicating that the overall conformational effects induced by dmg-PNA-T units in the derived PNA complexes with cDNA seem to be only marginal.


(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)

Figure 6. CD spectra of (A) aedmg-PNA2:DNA triplexes and (B) apdmg-PNA:DNA triplexes. The number shown above each curve refers to the PNA sequence shown in Table 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Figure 6. CD spectra of (A) aedmg-PNA2:DNA triplexes and (B) apdmg-PNA:DNA triplexes. The number shown above each curve refers to the PNA sequence shown in Table 1.
Mentions: In order to examine if aedmg-PNAs have any significant differences in their overall conformational features, the CD spectra of PNA complexes with DNA were examined (Fig. 6). The PNA2:DNA triplexes exhibit two maxima at 260 nm and 280 nm, a minimum at 246 nm and crossover points around 250 nm. The double hump profile in the region 260–280 nm is characteristic of polyT-polyA:polyT (PNA2:DNA) triplexes.28 The CD profiles of dmg-PNA:DNA duplexes were similar to those of the control achiral aeg-PNA:DNA duplexes indicating that the overall conformational effects induced by dmg-PNA-T units in the derived PNA complexes with cDNA seem to be only marginal.

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