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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 5. First derivative UV absorbance-temp plots of PNA:DNA duplexes. p and ap refer to parallel and antiparallel duplexes. For PNA numbers see Table 1.
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Figure 5: Figure 5. First derivative UV absorbance-temp plots of PNA:DNA duplexes. p and ap refer to parallel and antiparallel duplexes. For PNA numbers see Table 1.

Mentions: The PNA:DNA and PNA:RNA duplexes differ in conformation and structural features compared with PNA2:DNA and PNA2:RNA triplexes,10 and hence the mixed base sequence aeg (12), aedmg (13) and apdmg (14) PNAs were examined for their duplex forming abilities with antiparallel (ap) cDNA 17 and RNA 20 sequences (Fig. 5). PNAs with mixed base purine-pyrimidine sequences can form duplexes also in parallel orientations (parallel: N-terminus of PNA aligned with 5′ of DNA/RNA; antiparallel: N-terminus of PNA aligned with 3′-end of DNA/RNA) and hence this possibility was examined with parallel (p) cDNA 18 and RNA 21 oligonucleotides. This is not possible in triplexes wherein the identity of parallel-antiparallel binding orientation of the two PNA strands involved in complex formation cannot be distinguished.


(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 5. First derivative UV absorbance-temp plots of PNA:DNA duplexes. p and ap refer to parallel and antiparallel duplexes. For PNA numbers see Table 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Figure 5. First derivative UV absorbance-temp plots of PNA:DNA duplexes. p and ap refer to parallel and antiparallel duplexes. For PNA numbers see Table 1.
Mentions: The PNA:DNA and PNA:RNA duplexes differ in conformation and structural features compared with PNA2:DNA and PNA2:RNA triplexes,10 and hence the mixed base sequence aeg (12), aedmg (13) and apdmg (14) PNAs were examined for their duplex forming abilities with antiparallel (ap) cDNA 17 and RNA 20 sequences (Fig. 5). PNAs with mixed base purine-pyrimidine sequences can form duplexes also in parallel orientations (parallel: N-terminus of PNA aligned with 5′ of DNA/RNA; antiparallel: N-terminus of PNA aligned with 3′-end of DNA/RNA) and hence this possibility was examined with parallel (p) cDNA 18 and RNA 21 oligonucleotides. This is not possible in triplexes wherein the identity of parallel-antiparallel binding orientation of the two PNA strands involved in complex formation cannot be distinguished.

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