EXPRESSION OF BIOLOGICAL-ACTIVITY OF DRACULIN, THE ANTICOAGULANT FACTOR FROM VAMPIRE BAT SALIVA, IS STRICTLY DEPENDENT ON THE APPROPRIATE GLYCOSYLATION OF THE NATIVE MOLECULE

Draculin, a glycoprotein isolated from vampire bat (Desmodus rotundus) saliva, is a natural anticoagulant which inhibits activated coagulati on factors IX (IXa) and X (Xa). The observation that under captivity c onditions, the anticoagulant activity present in vampire bat saliva is dependent upon the salivation protocol, led us to investigate the pos sible relationship between the expression of biological activity of na tive draculin and the post-translational glycosylation of the protein backbone. Daily salivation of vampire bats yields a saliva that progre ssively decreases in anticoagulant activity, without any significant c hange in overall protein content, or in the amount of protein specific ally recognized by a polyclonal anti-draculin antibody. Anticoagulant activity of the saliva is restored after a 4-day period of rest. Besid es the marked difference in anticoagulant activity, purified native dr aculin, obtained from high- and low-activity saliva, shows significant differences in: (a) composition of the carbohydrate moiety, and (b) G lycosylation pattern. Furthermore, controlled chemical deglycosylation of native draculin, under conditions that do not affect the polypepti de backbone, progressively leads to complete loss of the biological ac tivity. Our present results implicate that correct glycosylation of dr aculin is a seminal event for the expression of the biological activit y of this glycoprotein. (C) 1998 Elsevier Science B.V. All rights rese rved.