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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2006-2-21
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pubmed:abstractText |
The first macrocyclic inhibitor of the Plasmodium falciparum aspartic proteases plasmepsin I, II, and IV with considerable selectivity over the human aspartic protease cathepsin D has been identified. A series of macrocyclic compounds were designed and synthesized. Cyclizations were accomplished using ring-closing metathesis with the second generation Grubbs catalyst. These compounds contain either a 13-membered or a 16-membered macrocycle and incorporate a 1,2-dihydroxyethylene as transition state mimicking unit. The binding mode of this new class of compounds was predicted with automated docking and molecular dynamics simulations, with an estimation of the binding affinities through the linear interaction energy (LIE) method.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0968-0896
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pubmed:author |
pubmed-author:ClementeJose CJC,
pubmed-author:DunnBen MBM,
pubmed-author:ErsmarkKarolinaK,
pubmed-author:GogollAdolfA,
pubmed-author:Gutiérrez-de-TeránHugoH,
pubmed-author:HallbergAndersA,
pubmed-author:HamelinkElizabethE,
pubmed-author:JankaLinda KLK,
pubmed-author:NervallMartinM,
pubmed-author:QvistJohanJ,
pubmed-author:SamuelssonBertilB
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2197-208
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16307884-Animals,
pubmed-meshheading:16307884-Aspartic Acid Endopeptidases,
pubmed-meshheading:16307884-Binding, Competitive,
pubmed-meshheading:16307884-Binding Sites,
pubmed-meshheading:16307884-Cathepsin D,
pubmed-meshheading:16307884-Crystallography, X-Ray,
pubmed-meshheading:16307884-Cyclization,
pubmed-meshheading:16307884-Drug Design,
pubmed-meshheading:16307884-Humans,
pubmed-meshheading:16307884-Macrocyclic Compounds,
pubmed-meshheading:16307884-Models, Chemical,
pubmed-meshheading:16307884-Models, Molecular,
pubmed-meshheading:16307884-Molecular Conformation,
pubmed-meshheading:16307884-Plasmodium falciparum,
pubmed-meshheading:16307884-Protease Inhibitors,
pubmed-meshheading:16307884-Protozoan Proteins,
pubmed-meshheading:16307884-Structure-Activity Relationship
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pubmed:year |
2006
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pubmed:articleTitle |
Macrocyclic inhibitors of the malarial aspartic proteases plasmepsin I, II, and IV.
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pubmed:affiliation |
Department of Medicinal Chemistry, Uppsala University, BMC, PO Box 574, SE-751 23 Uppsala, Sweden.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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