title: Variabilin, a novel RGD-containing antagonist of glycoprotein IIb-IIIa and platelet aggregation inhibitor from the hard tick Dermacentor variabilis.
abstract: A novel inhibitor of human platelet aggregation, named variabilin, was isolated from salivary glands of the hard tick Dermacentor variabilis using a combination of gel filtration and high pressure liquid chromatography. Variabilin was a potent antagonist of the fibrinogen receptor glycoprotein IIb-IIIa (GPIIb-IIIa; alphaIIbbeta3) and the vitronectin receptor alphavbeta3. Amino acid sequence analysis by Edman degradation revealed that it has 47 residues, with a molecular weight of 4968.5. Like many other naturally occurring antagonists of GPIIb-IIIa, variabilin contains the RGD (Arg-Gly-Asp) motif. However, unlike the RGD-containing antagonists of GPIIb-IIIa, the RGD sequence of variabilin is not positioned in a loop bracketed by cysteine residues. It has little sequence homology to the other known naturally occurring antagonists of GPIIb-IIIa, including the disintegrins from snakes, decorsin and ornatin from leeches, and disagregin from soft ticks. Variabilin is the first RGD-containing antagonist isolated from ticks.
authors.affiliation: Department of Biology, University of Memphis, Memphis, Tennessee 38152, USA.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: L B
authors.initials: LB
authors.lastname: Coons
authors.forename: D B
authors.initials: DB
authors.lastname: Taylor
authors.forename: S E
authors.initials: SE
authors.lastname: Stevens
authors.forename: T K
authors.initials: TK
authors.lastname: Gartner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003870:Dermacentor / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D012469:Salivary Glands / Q000737:chemistry*; D017421:Sequence Analysis
chemical_list: D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011506:Proteins; C100625:variabilin; C047981:arginyl-glycyl-aspartic acid