Specific inhibition of binding of antistasin and [A103,106,108] antistasin 93-119 to sulfatide (Gal(3-SO4)beta 1-1Cer) by glycosaminoglycans.
Leech-derived antistasin is a potent anticoagulant and antimetastatic protein that binds sulfatide (Gal(3-SO4)beta 1-1Cer) and sulfated polysaccharides. In this study, the synthetic fragment [A103,106,108] antistasin 93-119, which corresponds to the carboxyl terminus, showed specific and saturable binding to sulfatide. Binding was competitively blocked by glycosaminoglycans (GAGs) in the order: dextran sulfate 5000 congruent to dextran sulfate 500,000 greater than heparin greater than dermatan sulfate much greater than chondroitin sulfates A and C. This rank order of inhibitory potency was identical to that observed with whole antistasin. We suggest that residues 93-119 of antistasin represent a critical domain for binding GAGs and sulfated glycolipids.
Brankamp
R G
RG
Marion Merrell Dow Research Institute, Cincinnati, OH 45215.
Manley
G D
GD
Owen
T J
TJ
Krstenansky
J L
JL
Cardin
A D
AD
D000818:Animals; D002809:Chondroitin Sulfates / Q000494:pharmacology; D003871:Dermatan Sulfate / Q000494:pharmacology; D016264:Dextran Sulfate / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D007447:Invertebrate Hormones / Q000378:metabolism*; D007865:Leeches; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D013433:Sulfoglycosphingolipids / Q000378:metabolism*
D006025:Glycosaminoglycans; D007447:Invertebrate Hormones; D010446:Peptide Fragments; D013433:Sulfoglycosphingolipids; C072606:galactosyl-(3-sulfo)-1-ceramide; C053155:antistasin; D003871:Dermatan Sulfate; D006493:Heparin; D002809:Chondroitin Sulfates; D016264:Dextran Sulfate