Design and synthesis of imidazole conjugated pna and polypeptides as nuclease mimics

Abstract

The imidazole moiety is incorporated on PNA monomers by replacing the base withimidazole All monomers were characterized by 1H and 13C NMR spectroscopy massspectral analysis and other appropriate analytical data The rationally designed modifiedPNA monomers have been incorporated into 10 mer pyrimidine and 9 mer and 12 mermixed purine pyrimidine PNA sequence The PNA oligomers after cleavage werepurified by RP HPLC and characterized by MALDI TOF spectrometry Duplexes fromall imidazolyl PNAs with complementary antiparallel DNA showed significantdestabilisation with all natural nucleobases in cDNA In case of antiparallel PNA PNAduplexes 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 ofparallel PNA PNA duplexes all imidazolyl PNAs showed G to be more compatibleagainst imidazole modifications and stabilise corresponding duplex better than other threenucleobases A C and T The NH Boc aminoethyl N imidazole N1 acetamido ethylglycinate and NH Boc aminoethyl N imidazole C4 acetamido ethyl glycinatemonomers showed selective metal complex with Cu2 and Zn2 respectively and thethermal stability Tm of PNA PNA duplexes of Im N1 PNA 1 and Im C4 PNA 2 aresignificantly increased 5 186 C specifically in presence of Cu2 and Zn2 respectively Intriplex and half duplex UImT10 PNA 4 2 RNA 1 947 CImT10 PNA 5 2 RNA 1 and Bis Im PNA 6 RNA 1 the imidazole modified PNAs cleaved 10 RNA 1 in the absence ofmetal salts and in presence of metal salt cleavage increased upto the 20 With duplexesUIm PNA 7 RNA 1 RNA 2 and 947 CIm PNA 8 RNA 2 RNA 3 the imidazole modifiedPNAs did not cleave RNA 2 RNA 3 in presence or absence of Zn2 metal ions but RNA2 RNA 3 partial degradation was observed only in presnsce of only Zn2 ion Further theimidazolyl 4 aminoproline peptides were studied for the RNA newline newline