Spermine conjugated peptide nucleic acids (spPNA): UV and fluorescence studies of PNA-DNA hybrids with improved stability.
Peptide Nucleic Acids (PNAs), the achiral DNA mimics with amide backbone, are emerging as attractive leads for drug development by antisense approach. Two major limitations of PNAs from an application perspective are their limited solubility in aqueous systems and pronounced self-organization. In this paper, it is shown that covalent conjugation of spermine at C-terminus of PNA (spPNA) improves its solubility and binds to complementary DNA 20 times stronger than the corresponding binding of PNA. Fluorescence kinetics shows a 2 fold acceleration of the bimolecular association process in spPNA:DNA hybrids, due to electrostatic interaction cationic spermine tagged to PNA with anionic DNA. This modification is easy to incorporate into PNA synthetic protocols to make them more effective in biological applications and may improve the poor cell uptake of PNA.
Gangamani
B P
BP
Organic Chemistry Synthesis Division, National Chemical Laboratory, Pune, India. f1p4
Kumar
V A
VA
Ganesh
K N
KN
D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D004355:Drug Stability; D005470:Fluorometry; D007700:Kinetics; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011119:Polynucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D013096:Spermine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature
D009838:Oligodeoxyribonucleotides; D010455:Peptides; D011119:Polynucleotides; D013096:Spermine; D004247:DNA