Conversion of a polysaccharide to nitric oxide-releasing form. Dual-mechanism anticoagulant activity of diazeniumdiolated heparin.
We describe heparin/diazeniumdiolate conjugates that generate nitric oxide (NO) at physiological pH. Like the heparin from which they were prepared, they inhibit thrombin-induced blood coagulation. Unlike heparin, they can also inhibit and reverse ADP-induced platelet aggregation (as expected for an NO-releasing agent), suggesting potential utility as dual-action antithrombotics.
Saavedra
J E
JE
Intramural Research Support Program, SAIC Frederick, NCI-FCRDC, MD 21702, USA.
Mooradian
D L
DL
Mowery
K A
KA
Schoenfisch
M H
MH
Citro
M L
ML
Davies
K M
KM
Meyerhoff
M E
ME
Keefer
L K
LK
D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology*; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009569:Nitric Oxide / Q000737:chemistry*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011134:Polysaccharides / Q000737:chemistry*
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D011134:Polysaccharides; D009569:Nitric Oxide; D006493:Heparin