Protein Structure Similarity as Guiding Principle for Combinatorial Library Design
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M. A. Koch
Abstract
Proteins are modularly built from a limited set of approximately 1000 structural domains. The evolutionary relationship within a domain family suggests that the knowledge about a common fold structure can be exploited for the design of small molecule libraries in the development of inhibitors and ligands. This principle has been used for the synthesis of inhibitors for kinases sharing the same fold. It can also be applied for proteins which share the same fold architecture yet belong to different functional classes. Bestatin – originally known as an aminopeptidase inhibitor – was employed as guiding structure for the development of leukotriene A4 hydrolase inhibitors. A combinatorial approach helped to identify inhibitors for sulfotransferases which share structural similarity with nucleotide kinases using a kinase inhibitor core structure as guiding principle.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
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- Paper of the Year 2002
- Terminal Differentiation of Epithelia
- Use of Detergents to Study Membrane Rafts: The Good, the Bad, and the Ugly
- Protein Structure Similarity as Guiding Principle for Combinatorial Library Design
- The Making of a Professional Secretory Cell: Architectural and Functional Changes in the ER during B Lymphocyte Plasma Cell Differentiation
- No Superoxide Dismutase Activity of Cellular Prion Protein in vivo
- A Nucleosome-Free dG-dC-Rich Sequence Element Promotes Constitutive Transcription of the Essential Yeast RIO1 Gene
- Phosphatidylinositol-3,5-Bisphosphate Is a Potent and Selective Inhibitor of Acid Sphingomyelinase
- Function and Structure of N-Terminal and C-Terminal Domains of Calcineurin B Subunit
- Verification of the Interaction of a Tryparedoxin Peroxidase with Tryparedoxin by ESI-MS/MS
- Kinin-B1 Receptors in Ischaemia-Induced Pancreatitis: Functional Importance and Cellular Localisation
- Bioactivatable, Membrane-Permeant Analogs of Cyclic Nucleotides as Biological Tools for Growth Control of C6 Glioma Cells
- Human Cathepsin H: Deletion of the Mini-Chain Switches Substrate Specificity from Aminopeptidase to Endopeptidase
- Nitridergic Platelet Pathway Activation by Hementerin, a Metalloprotease from the Leech Haementeria depressa
Articles in the same Issue
- Paper of the Year 2002
- Terminal Differentiation of Epithelia
- Use of Detergents to Study Membrane Rafts: The Good, the Bad, and the Ugly
- Protein Structure Similarity as Guiding Principle for Combinatorial Library Design
- The Making of a Professional Secretory Cell: Architectural and Functional Changes in the ER during B Lymphocyte Plasma Cell Differentiation
- No Superoxide Dismutase Activity of Cellular Prion Protein in vivo
- A Nucleosome-Free dG-dC-Rich Sequence Element Promotes Constitutive Transcription of the Essential Yeast RIO1 Gene
- Phosphatidylinositol-3,5-Bisphosphate Is a Potent and Selective Inhibitor of Acid Sphingomyelinase
- Function and Structure of N-Terminal and C-Terminal Domains of Calcineurin B Subunit
- Verification of the Interaction of a Tryparedoxin Peroxidase with Tryparedoxin by ESI-MS/MS
- Kinin-B1 Receptors in Ischaemia-Induced Pancreatitis: Functional Importance and Cellular Localisation
- Bioactivatable, Membrane-Permeant Analogs of Cyclic Nucleotides as Biological Tools for Growth Control of C6 Glioma Cells
- Human Cathepsin H: Deletion of the Mini-Chain Switches Substrate Specificity from Aminopeptidase to Endopeptidase
- Nitridergic Platelet Pathway Activation by Hementerin, a Metalloprotease from the Leech Haementeria depressa
