Document Detail


In silico fragment-based discovery of DPP-IV S1 pocket binders.
MedLine Citation:
PMID:  16321524     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dipeptidyl peptidase IV is a clinically validated target for type-2 diabetes and belongs to a family of peptidases with a quite unique post-proline cleavage specificity. Known inhibitors contain a limited number of molecular anchors occupying the small prototypical S1 pocket. A virtual screening approach for such S1-binding fragments was carried out using FlexX docking to evaluate its potential to confirm known and find novel compounds. Several low molecular weight inhibitors exhibiting activities in the micromolar range could be identified as starting points for structure-based design.
Authors:
Christian Rummey; Sonja Nordhoff; Meinolf Thiemann; Günther Metz
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  16     ISSN:  0960-894X     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-01-27     Completed Date:  2006-03-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  1405-9     Citation Subset:  IM    
Affiliation:
Computational Discovery, Santhera Pharmaceuticals, Im Neuenheimer Feld 518-519, 69120 Heidelberg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD26 / chemistry*,  metabolism*
Binding Sites
Computational Biology*
Crystallography, X-Ray
Drug Design*
Drug Evaluation, Preclinical / methods*
Inhibitory Concentration 50
Models, Molecular
Molecular Weight
Protease Inhibitors / chemistry*,  metabolism*,  pharmacology
Protein Structure, Tertiary
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Protease Inhibitors; EC 3.4.14.5/Antigens, CD26

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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