Inhibition of platelet heparitinase by phosphorothioate DNA oligonucleotides.
In view of the role that heparitinase and heparanase enzymes are thought to play in regulating the proliferation of smooth muscle cells, inhibitors of these enzymes may have therapeutic value in the treatment of vascular hyperplasia. Here we report that phosphorothioate oligodeoxynucleotides inhibit platelet heparitinase and related enzymes in vitro. The inhibition is greatly enhanced by the presence of a GGG motif in the oligonucleotide, and also increases with oligonucleotide for two phosphorothioate DNA 30-mers consisting solely of guanosine and thymidine nucleotides. Their inhibitory efficacy was greater when heparan sulphate was used as substrate.
Graham
L D
LD
CSIRO Division of Biomolecular Engineering, Sydney Laboratory, North Ryde, NSW, Australia.
Mitchell
S M
SM
Underwood
P A
PA
D001483:Base Sequence; D001792:Blood Platelets / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000494:pharmacology*; D011133:Polysaccharide-Lyases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013873:Thionucleotides / Q000138:chemical synthesis / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D013873:Thionucleotides; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase