This invention relates to peptides which inhibit the binding of von Willebrand Factor (vWF) to Factor VIII (FVIII).
vWF and FVIII both have important but different functions in the maintenance of hemostasis. vWF participates in platelet-vessel wall interactions at the site of vascular injury whereas FVIII accelerates the activation of Factor X by Factor IXa in the presence of platelets and calcium ions. vWF and FVIII circulate in plasma as a noncovalently linked complex thought to be held together by both electrostatic and hydrophobic forces. vWF is thought to stabilize FVIII in vitro and prolong its half-life in the circulation. Consequently, in the absence of endogeneous vWF the circulating half-life of FVIII is markedly reduced. Since FVIII participates in the intrinsic Pathway of blood coagulation, agents capable of interferinglittle remnants of their native land. The indigenous bison herd, sixty million or more strong at one time, was down to a few hundred stragglers. The ecosystem of the high plains, which had been compared to Eden by Lewis and Clark, was being torn to pieces. Where birds had once blotted the skies of migratory flyways, it was hard at times to find a single duck on a fall afternoon. But even with the smell of death on it, the land made Roosevelt whole again. He found renewal in wilderness—the geography of hope, as it was called by westerners who followed him.

Back in Manhattan after two years, Roosevelt resumed his political career. He ran for mayor of New York City in 1886, and lost, but considered the whole