title: Design of Potent and Highly Selective Inhibitors for Human β-Secretase 2 (Memapsin 1), a Target for Type 2 Diabetes.
abstract: Design, synthesis and evaluation of very potent and selective β-Secretase 2 (memapsin 1, BACE 2) inhibitors are described. The inhibitors were designed specifically to interact with the S2'-site of β-secretase 2 to provide >170,000-fold selectivity over β-secretase (BACE 1) and >15,000-fold selectivity over cathepsin D. BACE 2 is implicated in Type 2 diabetes. The studies serve as an important guide to selective BACE 2 inhibitors.
authors.affiliation: Department of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907 (USA).
authors.forename: Arun K
authors.initials: AK
authors.lastname: Ghosh
authors.affiliation: Department of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907 (USA).
authors.forename: Bhavanam Sekhara
authors.initials: BS
authors.lastname: Reddy
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907 (USA).
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Yen
authors.affiliation: Department of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907 (USA).
authors.forename: Emilio
authors.initials: E
authors.lastname: Cardenas
authors.affiliation: Department of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907 (USA).
authors.forename: Kalapala Venketeswara
authors.initials: KV
authors.lastname: Rao
authors.affiliation: Protein Studies Program, Oklahoma Medical Research Foundation, University of Oklahoma, Oklahoma City, OK 73104 (USA).
authors.forename: Deborah
authors.initials: D
authors.lastname: Downs
authors.affiliation: Protein Studies Program, Oklahoma Medical Research Foundation, University of Oklahoma, Oklahoma City, OK 73104 (USA).
authors.forename: Xiangping
authors.initials: X
authors.lastname: Huang
authors.affiliation: Protein Studies Program, Oklahoma Medical Research Foundation, University of Oklahoma, Oklahoma City, OK 73104 (USA).
authors.forename: Jordan
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907 (USA); Department of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907 (USA); Department of Biochemistry, Purdue University, West Lafayette, IN 47907 (USA).
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mesecar