Discovery of Thrombin Inhibitor Fragments from Chemical Microarray Screening

Authors: Neumann, Thomas; Junker, Hans-Dieter; Keil, Oliver; Burkert, Klaus; Ottleben, Holger; Gamer, Jurgen; Sekul, Renate; Deppe, Holger; Feurer, Achim; Tomandl, Dirk; Metz, Gunther

Source: Letters in Drug Design & Discovery, Volume 2, Number 8, December 2005 , pp. 590-594(5)

Publisher: Bentham Science Publishers

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Abstract:

Surface plasmon resonance imaging, a low affinity screening method, allows the highly parallel detection of small molecules binding to a target protein. The screening of a fragment based compound library immobilized on chemical microarrays resulted in the discovery of binding fragments for the serine protease thrombin. Functional assays confirmed enzymatic inhibition of microarray hits and crystallography established the binding mode of a non-basic S1 motif providing a starting point for medicinal chemistry.

Keywords: Fragment discovery; chemical microarrays; surface plasmon resonance; thrombin; non-basic S1 binder

Document Type: Review article

DOI: http://dx.doi.org/10.2174/157018005774717343

Affiliations: 1: Computational Discovery, Santhera Pharmaceuticals, Im Neuenheimer Feld 518-519, 69120 Heidelberg, Germany.

Publication date: 2005-12-01

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Letters in Drug Design & Discovery publishes original letters on all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis will be on publishing quality papers very rapidly. Letters will be processed rapidly by taking full advantage of Internet technology for both the submission and review of manuscripts. The journal is essential reading to all pharmaceutical scientists involved in research in drug design and discovery.