Design and synthesis of statine-based cell-permeable peptidomimetic inhibitors of human beta-secretase.
J Med Chem
; 46(10): 1799-802, 2003 May 08.
Article
em En
| MEDLINE
| ID: mdl-12723942
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Ácido Aspártico Endopeptidases
/
Inibidores Enzimáticos
/
Aminoácidos
Limite:
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos