Synthesis and evaluation of some properties of chimeric oligomers containing PNA and phosphono-PNA residues.
In an attempt to improve physico-chemical and biological properties of peptide nucleic acids (PNAs), particularly water solubility and cellular uptake, the synthesis of chimeric oligomers consisted of PNA and phosphono-PNA analogues (pPNAs) bearing the four natural nucleobases has been accomplished. To produce these chimeras, pPNA monomers of two types containing N-(2-hydroxyethyl)phosphonoglycine, or N-(2-aminoethyl)phosphonoglycine backbone, were used in conjunction with PNA monomers representing derivatives of N-(2-aminoethyl)glycine, or N-(2-hydroxyethyl)glycine. The oligomers obtained were composed of either PNA and pPNA stretches or alternating PNA and pPNA monomers. The examination of hybridization properties of PNA-pPNA chimeras to DNA and RNA complementary strands in comparison with pure PNAs, and pPNAs as well as DNA-pPNA hybrids and DNA fragments confirmed that these chimeras form stable complexes with complementary DNA and RNA fragments. They were found to be resistant to degradation by nucleases. All these properties together with good solubility in water make PNA-pPNA hybrids promising for further evaluation as potential therapeutic agents.
Efimov
V A
VA
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, ul. Miklukho-Maklaya 16/10, Moscow 117871, Russia. eva@ibch.siobc.ras.ru
Choob
M V
MV
Buryakova
A A
AA
Kalinkina
A L
AL
Chakhmakhcheva
O G
OG
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018076:DNA, Complementary / Q000737:chemistry; D019281:Dimerization; D004355:Drug Stability; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D006358:Hot Temperature; D009693:Nucleic Acid Hybridization; D009696:Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D009757:Nylons / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis*; D063065:Organophosphonates / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D018075:RNA, Complementary / Q000737:chemistry; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D012995:Solubility; D014466:Ultraviolet Rays
D018076:DNA, Complementary; D009696:Nucleic Acids; D009757:Nylons; D009841:Oligonucleotides; D063065:Organophosphonates; D010455:Peptides; D018075:RNA, Complementary; C028791:N-(2-aminoethyl)glycine; D015719:Single-Strand Specific DNA and RNA Endonucleases; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I; D005998:Glycine