Disintegrins and other naturally occurring antagonists of platelet fibrinogen receptors.
Disintegrins represent a family of low-molecular weight, cysteine-rich, RGD-containing peptides that inhibit fibrinogen binding to glycoprotein IIb/IIIa complex as well as binding of other ligands to RGD-dependent integrins on the surface of other cells. Disintegrins occur in the venom of various vipers. Disintegrin domains have been identified in viper venom hemorrhagins and in sperm proteins involved in the sperm-egg fusion. Amino acid sequences of 25 disintegrins, alignment of S-S bridges in four disintegrins, and stereo models of five disintegrins are presented. Primary structures of disintegrins differ significantly from other fibrinogen receptor antagonists occurring in the venoms of Elapidae, leeches, and ticks. Several aspects of structure-function relationship of disintegrins, their biological activities, and possible clinical applications are discussed.
Niewiarowski
S
S
Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140.
McLane
M A
MA
Kloczewiak
M
M
Stewart
G J
GJ
D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000502:physiology*; D019483:Disintegrins; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D014688:Venoms
D019483:Disintegrins; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D014688:Venoms