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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2004-3-30
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pubmed:abstractText |
(Hydroxyethyl)urea peptidomimetics are potent inhibitors of gamma-secretase that are accessible in a few synthetic steps. Systematic alteration of P2-P4' revealed that the corresponding S2-S4' active site pockets accommodate a variety of substituents, consistent with the fact that this protease cleaves a variety of single-pass membrane proteins; however, phenylalanine is not well tolerated at P2'. A compound spanning P2-P3' was identified as a low nM inhibitor of gamma-secretase activity both in cells and under cell-free conditions.
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pubmed:grant |
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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 |
0960-894X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
19
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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 |
1935-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15050631-Amyloid Precursor Protein Secretases,
pubmed-meshheading:15050631-Animals,
pubmed-meshheading:15050631-Binding Sites,
pubmed-meshheading:15050631-Biomimetic Materials,
pubmed-meshheading:15050631-CHO Cells,
pubmed-meshheading:15050631-Cricetinae,
pubmed-meshheading:15050631-Endopeptidases,
pubmed-meshheading:15050631-Hydroxyurea,
pubmed-meshheading:15050631-Molecular Structure,
pubmed-meshheading:15050631-Peptide Fragments,
pubmed-meshheading:15050631-Protease Inhibitors,
pubmed-meshheading:15050631-Structure-Activity Relationship
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pubmed:year |
2004
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pubmed:articleTitle |
Probing pockets S2-S4' of the gamma-secretase active site with (hydroxyethyl)urea peptidomimetics.
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pubmed:affiliation |
Center for Neurologic Diseases, Harvard Medical School and Brigham and Womens Hospital, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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