Design and synthesis of statine-based cell-permeable peptidomimetic inhibitors of human beta-secretase.
Basic Information
ID: ALA1145027
Journal: J Med Chem
Title: Design and synthesis of statine-based cell-permeable peptidomimetic inhibitors of human beta-secretase.
Authors: Hom RK, Fang LY, Mamo S, Tung JS, Guinn AC, Walker DE, Davis DL, Gailunas AF, Thorsett ED, Sinha S, Knops JE, Jewett NE, Anderson JP, John V.
Abstract: We describe the development of statine-based peptidomimetic inhibitors of human beta-secretase (BACE). The conversion of the peptide inhibitor 1 into cell-permeable peptidomimetic inhibitors of BACE was achieved through an iterative strategy of conceptually subdividing 1 into three regions: an N-terminal portion, a central statine-containing core, and a C-terminus. Replacement of the amino acid residues of 1 with moieties with less peptidic character was done with retention of BACE enzyme inhibitory activity. This approach led to the identification of the cell-permeable BACE inhibitor 38 that demonstrated BACE-mechanism-selective inhibition of Abeta secretion in human embryonic kidney cells.
CiteXplore: 12723942
DOI: 10.1021/jm025619l
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