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Conformation of a Bound Inhibitor of Blood Coagulant Factor Xa^†

Daniel R. Studelska,^‡^§ Lynda M. McDowell,^‡ Marc Adler, Robert D. O'Connor,^‡ Anil K. Mehta,^‡ William J. Guilford, Jerry L. Dallas, Damian Arnaiz, David R. Light, and Jacob Schaefer*^‡

Department of Chemistry, Washington University, St. Louis, Missouri 63130, and Berlex Biosciences, 2600 Hilltop Drive, Richmond, California 94804

Biochemistry, 2003, 42 (26), pp 7942–7949

DOI: 10.1021/bi027369g

Publication Date (Web): June 17, 2003

Abstract

¹³C{¹⁵N} and ¹³C{¹⁹F} rotational-echo double-resonance NMR have been used to characterize the enzyme-bound structure of ZK-816042, an amidine−imidazoline inhibitor of human factor Xa (FXa). The NMR experiments were performed on a lyophilized FXa−inhibitor complex. The complex was formed in solution in the presence of stabilizing excipients and frozen after gradual supercooling prior to lyophilization. The results indicate that the inhibitor binds with a distribution of orientations of the imidazoline ring.

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