Abstract:
The imidazole moiety is incorporated on PNA monomers by replacing the base with
imidazole. All monomers were characterized by 1H & 13C NMR spectroscopy, mass
spectral analysis and other appropriate analytical data. The rationally designed modified
PNA monomers have been incorporated into 10-mer pyrimidine and, 9-mer and 12-mer
mixed purine- pyrimidine PNA sequence. The PNA oligomers after cleavage were
purified by RP-HPLC and characterized by MALDI-TOF spectrometry. Duplexes from
all imidazolyl PNAs with complementary antiparallel DNA showed significant
destabilisation with all natural nucleobases in cDNA. In case of antiparallel PNA:PNA
duplexes, these imidazolyl PNAs showed more stability with complementary G and A PNAs
PNAs whereas, T and C PNAs showed significantly less stable duplexes. In case of
parallel PNA:PNA duplexes, all imidazolyl PNAs showed G to be more compatible
against imidazole modifications and stabilise corresponding duplex better than other three
nucleobases A, C and T. The NH-Boc-aminoethyl-N-(imidazole-N1-acetamido) ethyl
glycinate and NH-Boc-aminoethyl-N-(imidazole-C4-acetamido) ethyl glycinate
monomers showed selective metal complex with Cu2+ and Zn2+ respectively and the
thermal stability (Tm) of PNA:PNA duplexes of Im(N1)-PNA 1 and Im(C4)-PNA 2 are
significantly increased 5 ºC specifically in presence of Cu2+ and Zn2+ respectively. In
triplex and half duplex (UImT10-PNA 4)2:RNA 1, (γCImT10-PNA 5)2:RNA 1 and Bis-Im-
PNA 6:RNA 1, the imidazole modified PNAs cleaved 10% RNA 1 in the absence of
metal salts and in presence of metal salt cleavage increased upto the 20%. With duplexes
UIm-PNA 7:RNA 1/RNA 2 and γCIm-PNA 8:RNA 2/RNA 3, the imidazole modified
PNAs did not cleave RNA 2/ RNA 3 in presence or absence of Zn2+ metal ions, but RNA
2/ RNA 3 partial degradation was observed only in presnsce of only Zn2+ ion. Further, the
imidazolyl-4-aminoproline peptides were studied for the RNA hydrolysis in presence and
absence of metal; however, they did not cause any significant degradation (observed
degradation less than 10%) of RNA 1 in the absence or in presence of Zn salt.
