Transition-metal complexes as inhibitors of proteins recognizing double-stranded fragments of nucleic acids.
A 30-membered DNA duplex containing the recognition site of restriction endonuclease SsoII and a 30-membered RNA--DNA hybrid duplex, a substrate of E. coli RNase H, were synthesized. The cleavage of the 30-membered fragments of nucleic acids catalyzed by endonucleases in the presence of Co-phthalocyanine complex [CoPc(COONa)8] containing eight carboxyl groups at the periphery of the ligand was studied. It was shown that the efficiency of enzyme catalysis decreases in the presence of the metal complex for both endonucleases. By addition of a 100-fold excess of Co-phthalocyanine complex with respect to DNA duplex the initial rate of substrate hydrolysis by restriction endonuclease SsoII is observed to decrease twice. An equimolar ratio of the metal complex and hybrid duplex leads to essentially complete inhibition of RNA cleavage by RNase H from E. coli. The inhibition of catalytic activity of enzymes recognizing the double-stranded nucleic acids in the presence of Co-phthalocyanine complex is assumed to be caused by the ability of the latter to interact with DNA, RNA, and DNA--RNA duplexes.
Krynetskaya
N F
NF
School of Chemistry, Lomonosov Moscow State University, Moscow, 119899, Russia.
Kubareva
E A
EA
Timchenko
M A
MA
Belkov
V M
VM
Shabarova
Z A
ZA
D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008670:Metals / Q000494:pharmacology*; D009696:Nucleic Acids / Q000737:chemistry / Q000378:metabolism*; D009942:Organometallic Compounds / Q000494:pharmacology; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D016914:Ribonuclease H / Q000037:antagonists & inhibitors / Q000378:metabolism; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D007211:Indoles; D008670:Metals; D009696:Nucleic Acids; D009942:Organometallic Compounds; D011506:Proteins; C063633:cobalt phthalocyanine; D012313:RNA; D004247:DNA; C045297:CCNGG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; D016914:Ribonuclease H