title: Rational design and synthesis of highly potent pharmacological chaperones for treatment of N370S mutant Gaucher disease.
abstract: Highly potent N-substituted delta-lactams have been rationally designed and synthesized by a concise route with a one-pot tandem reaction as key step. These iminosugars show weak inhibition of wild-type beta-glucocerebrosidase but 3- to 6-fold increases in mutant enzyme activity (N370S).
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China.
authors.forename: Guan-Nan
authors.initials: GN
authors.lastname: Wang
authors.forename: Gabriele
authors.initials: G
authors.lastname: Reinkensmeier
authors.forename: Si-Wei
authors.initials: SW
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Liang-Ren
authors.initials: LR
authors.lastname: Zhang
authors.forename: Li-He
authors.initials: LH
authors.lastname: Zhang
authors.forename: Terry D
authors.initials: TD
authors.lastname: Butters
authors.forename: Xin-Shan
authors.initials: XS
authors.lastname: Ye
mesh_terms: D015195:Drug Design; D005776:Gaucher Disease / Q000188:drug therapy* / Q000235:genetics; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D050111:Imino Sugars / Q000138:chemical synthesis* / Q000494:pharmacology; D007769:Lactams / Q000138:chemical synthesis* / Q000494:pharmacology; D020125:Mutation, Missense; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D050111:Imino Sugars; D007769:Lactams; D005962:Glucosylceramidase