Limits...
(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.

Show MeSH

Related in: MedlinePlus

Figure 4. First derivative UV absorbance-temp plots of (A) aedmg-PNA2:DNA and (B) aedmg-PNA2:RNA triplexes. See Supplemental Material for corresponding data on apdmg-PNA2:DNA/RNA triplexes. The numbers associated with each curve corresponds to PNAs in Table 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3368815&req=5

Figure 4: Figure 4. First derivative UV absorbance-temp plots of (A) aedmg-PNA2:DNA and (B) aedmg-PNA2:RNA triplexes. See Supplemental Material for corresponding data on apdmg-PNA2:DNA/RNA triplexes. The numbers associated with each curve corresponds to PNAs in Table 1.

Mentions: The homothymine aeg-PNA sequences with cDNA-dA8 are known to form PNA2:DNA triplexes.1,2 The binding stoichiometry of aedmg-PNA-T8:DNA 15 complexes was established as 2:1 expected for a PNA2:DNA triplex from UV Job’s plot (see Supplemental Material).27 The thermal stabilities of triplexes from unmodified PNA 1 and dmg-PNA-T8 (PNA 2–11) with cDNA 15 and RNA 19 (polyrA40) were determined from temperature-dependent UV absorbance at 260 nm. The UV-Tm plots show a single sigmoidal transition, characteristic of PNA2:DNA triplex melting, wherein both the PNA strands dissociate simultaneously from DNA in a single step. The derivative plot of selected UV-melting data are shown in Figure 4 and the Tm values corresponding to peaks from such plots for various PNA2:DNA and PNA2:RNA triplexes of aedmg and apdmg-PNAs with cDNA 5 or RNA 19 are shown in Table 2.


(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 4. First derivative UV absorbance-temp plots of (A) aedmg-PNA2:DNA and (B) aedmg-PNA2:RNA triplexes. See Supplemental Material for corresponding data on apdmg-PNA2:DNA/RNA triplexes. The numbers associated with each curve corresponds to PNAs in Table 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Figure 4. First derivative UV absorbance-temp plots of (A) aedmg-PNA2:DNA and (B) aedmg-PNA2:RNA triplexes. See Supplemental Material for corresponding data on apdmg-PNA2:DNA/RNA triplexes. The numbers associated with each curve corresponds to PNAs in Table 1.
Mentions: The homothymine aeg-PNA sequences with cDNA-dA8 are known to form PNA2:DNA triplexes.1,2 The binding stoichiometry of aedmg-PNA-T8:DNA 15 complexes was established as 2:1 expected for a PNA2:DNA triplex from UV Job’s plot (see Supplemental Material).27 The thermal stabilities of triplexes from unmodified PNA 1 and dmg-PNA-T8 (PNA 2–11) with cDNA 15 and RNA 19 (polyrA40) were determined from temperature-dependent UV absorbance at 260 nm. The UV-Tm plots show a single sigmoidal transition, characteristic of PNA2:DNA triplex melting, wherein both the PNA strands dissociate simultaneously from DNA in a single step. The derivative plot of selected UV-melting data are shown in Figure 4 and the Tm values corresponding to peaks from such plots for various PNA2:DNA and PNA2:RNA triplexes of aedmg and apdmg-PNAs with cDNA 5 or RNA 19 are shown in Table 2.

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