Aventis Pharmaceuticals Inc.

Selectide Corporation

Other

Peter Strop

Marcel Patek

Martin Smrcina

Gary A Flynn

Armin Walser

Fahad A Al-Obeidi

Pavel Safar

Michal Lebl

James A Ostrem

Stephen A Baum

Safar Pavel

Eric Wegrzyniak

Alena Stierandova

Frantisek Turecek

Terry N Olney

Adi A Scheidemann

Frank J Schumacher, Iv

Daniel Schirlin

An apparatus and method for synthesizing a combinatorial library comprising a plurality of chemical compounds such that the chemical composition of each compound is easily tracked. The library compounds are synthesized on solid-phase supports, which are spatially arranged in frames during synthesis according to a predetermined protocol, such that each solid-phase support passes through a series of unique spatial 2D or 3D addresses by which the chemical composition of each compound may be determined at any point during synthesis. Solid-phase supports include hollow tubular-shaped lanterns and gears.

Apparatus and method for synthesizing combinatorial libraries

The invention provides compounds which specifically inhibit factor Xa activity having the structure A &mdash;A &mdash;(A ) &mdash;B, where m is 0 or 1. A compound of the invention is characterized, in part, in that it exhibits a specific inhibition of factor Xa activity with a K &lE;100 &mgr;M, preferably &lE;2 nM, and does not substantially inhibit the activity of other proteases involved in the coagulation cascade. The invention further provides methods of specifically inhibiting the activity of factor Xa and of inhibiting blood clotting in vitro and in an individual and methods of detecting factor Xa levels or activity.

Factor Xa inhibitors

The present invention provides an instrument and methods for the preparative separation of components of mixtures using mass spectrometric methods. Nondestructive ionization methods are employed to generate ionized components of a mixture, the ionized components are spatially separated by mass and the mass-separated ion components are trapped. The ion source and mass spectrometric techniques employed allow the generation of large ion currents of ion components, on the order of nanoamps, which facilitate rapid accumulation of nanomole quantities of mass-separated components in relatively short times (minutes to hours).

Preparative separation of mixtures by mass spectrometry

Apparatus and method for synthesizing combinational libraries

The invention provides compounds which specifically inhibit factor Xa activity. The compounds consist of the structure X.sub.1 -YIR-X.sub.2, wherein X.sub.1 is H, acyl, alkyl, acylalkyl, arylalkyl or one or more amino acids, and X.sub.2 is a modified C-terminal group, one or more carboxy-protecting groups or one or more amino acids or other substituent, and Y, I and R are tyrosine, isoleucine and arginine, respectively, or peptidomimetic or organic structures that possess the same functional activity as Y, I and R, respectively. In addition, the present invention provides a compound having the structure A1-A2-(A3).sub.m --B, where m is 0 or 1. A compound of the invention can be linear or cyclic and can be about 2 and 43 residues in length. A compound of the invention is characterized, in part, in that it exhibits a specific inhibition of factor Xa activity with a K.sub.i of .ltoreq.100 .mu.M, preferably .ltoreq.2 nM, and does not substantially inhibit the activity of other proteases involved in the coagulation cascade. The invention further provides methods of specifically inhibiting the activity of factor Xa and of inhibiting blood clotting in vitro and in an individual and methods of detecting factor Xa levels or activity.

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Tucson, AZ, United States of America

Peter Strop