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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
2008-9-19
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pubmed:databankReference |
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pubmed:abstractText |
A biosynthetic medicinal chemistry approach was applied to the optimization of the natural product Hsp90 inhibitor macbecin. By genetic engineering, mutants have been created to produce novel macbecin analogues including a nonquinone compound (5) that has significantly improved binding affinity to Hsp90 (Kd 3 nM vs 240 nM for macbecin) and reduced toxicity (MTD > or = 250 mg/kg). Structural flexibility may contribute to the preorganization of 5 to exist in solution in the Hsp90-bound conformation.
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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 |
Sep
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:BoydSusan MSM,
pubmed-author:CoatesNigel JNJ,
pubmed-author:FosterTeresa ATA,
pubmed-author:GaisserSabineS,
pubmed-author:GaitatzisNikolaosN,
pubmed-author:GregoryMatthew AMA,
pubmed-author:MartinChristine JCJ,
pubmed-author:MossSteven JSJ,
pubmed-author:Nur-E-AlamMohammadM,
pubmed-author:PearlLaurenceL,
pubmed-author:PeckGerrardG,
pubmed-author:ProdromouChrisostomosC,
pubmed-author:RadzomMarkusM,
pubmed-author:RoeS MarkSM,
pubmed-author:SheehanLesley SLS,
pubmed-author:SheridanRose MRM,
pubmed-author:VousdenWilliam AWA,
pubmed-author:WilkinsonBarrieB,
pubmed-author:ZhangMing-QiangMQ
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pubmed:issnType |
Electronic
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pubmed:day |
25
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5494-7
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
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pubmed:year |
2008
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pubmed:articleTitle |
Optimizing natural products by biosynthetic engineering: discovery of nonquinone Hsp90 inhibitors.
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pubmed:affiliation |
Biotica Technology Limited, Chesterford Research Park, Nr. Saffron Walden, Essex CB10 1XL, United Kingdom.
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pubmed:publicationType |
Journal Article
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