Stability of peptide nucleic acids in human serum and cellular extracts.
The stability of a new type of DNA mimic, peptide nucleic acid (PNA) in human blood serum, Eschericia coli and Micrococcus luteus extracts and nuclear and cytoplasmic extracts from mouse Ehrlich ascites tumor cells was investigated using HPLC analysis. Under conditions that caused complete cleavage of a control peptide, adrenocorticotropic hormone fragment 4-10, no significant degradation of the PNAs, H-T10-LysNH2 and H-TGTACGTCACAACTA-NH2, could be detected. Similarly, PNA H-T5-LysNH2 was found to resist attack by fungal proteinase K or porcine intestinal mucosa peptidase at concentrations exceeding those necessary to completely degrade a control peptide, H-Phe-Trp-Tyr-Cys-Phe-Trp-Tyr-Lys-Phe-Trp-Tyr-Lys-OH, by at least 1000- and 30-fold, respectively. Thus PNA is expected to have sufficient biostability to be used as a drug.
Demidov
V V
VV
Department of Medical Biochemistry & Genetics, Panum Institute, Copenhagen, Denmark.
Potaman
V N
VN
Frank-Kamenetskii
M D
MD
Egholm
M
M
Buchard
O
O
Sönnichsen
S H
SH
Nielsen
P E
PE
D000595:Amino Acid Sequence; D001483:Base Sequence; D001769:Blood; D015195:Drug Design; D004355:Drug Stability; D019286:Endopeptidase K; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010447:Peptide Hydrolases; D020135:Peptide Nucleic Acids; D012697:Serine Endopeptidases; D012995:Solubility; D014020:Tissue Extracts
D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D020135:Peptide Nucleic Acids; D014020:Tissue Extracts; C078138:peptide nucleic acid, T10-lysine; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases; D019286:Endopeptidase K