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Pseudodynamic Combinatorial Libraries: A Receptor-Assisted Approach for Drug Discovery

Authors

  • Andrew D. Corbett,

    1. Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montréal, QC, H3A 2 K6, Canada, Fax: (+1) 514-398-3797
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  • Jeremy D. Cheeseman,

    1. Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montréal, QC, H3A 2 K6, Canada, Fax: (+1) 514-398-3797
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  • Romas J. Kazlauskas Prof.,

    1. Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montréal, QC, H3A 2 K6, Canada, Fax: (+1) 514-398-3797
    2. Current address: University of Minnesota, Department of Biochemistry, Molecular Biology and Biophysics and The Biotechnology Institute, 1479 Gortner Avenue, Saint Paul, MN 55108, USA, Fax: (+1) 612-625-5780
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  • James L. Gleason Prof.

    1. Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montréal, QC, H3A 2 K6, Canada, Fax: (+1) 514-398-3797
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  • The authors thank FQRNT for support of this research through the Soutien aux Equipes and VRQ programs, Prof. Sidney M. Hecht (University of Virginia) for the discussion that led to this research, and Prof. Sijbren Otto, Prof. Jeremy K. M. Sanders, and Prof. K. Barry Sharpless for reading the manuscript.

Abstract

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Schutz vor Enzymen: Eine irreversible wässrige Festphasenpeptidkupplung führte zu einer Bibliothek aus acht Dipeptiden, die durch irreversible proteasekatalysierte Hydrolyse wieder zerstört werden. Dipeptide, die einen Komplex mit Carbonsäureanhydrase bilden, sind gegen Abbau geschützt. Durch wiederholte Addition des aktivierten Esters wurde nach sechs Zyklen ausschließlich das am stärksten koordinierende Dipeptid (>100:1) in 29 % Ausbeute erhalten.

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