title: 3D QSAR of novel estrogen-RGD peptide conjugates: getting insight into structural dependence of anti-osteoporosis activity and side effect of estrogen in ERT.
abstract: To explore the structural dependence of the oral potency and side effect of estrogen-RGD peptide conjugates, here six novel conjugates were prepared via introducing RGD-tetrapeptides into both 3- and 17-positions of estradiol, and introducing RGD-octapeptides into 3-position of estrone. In an ovariectomized mouse model they exhibited higher anti-osteoporosis activity and lower side effect than estrogen. For 3D QSAR analysis the anti-osteoporosis activities of nine known conjugates estrogen-RGD tetrapeptide conjugates were also provided. Using Cerius(2) module their 3D QSAR analysis was performed, four equations with high r(2) values were established, and the structural dependence of the oral potency and side effect of them was elucidated.
authors.affiliation: College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Jiangyuan
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Peng
authors.forename: Chunyu
authors.initials: C
authors.lastname: Li
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects*; D003198:Computer Simulation; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D006801:Humans; D051379:Mice; D008956:Models, Chemical; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D010024:Osteoporosis / Q000188:drug therapy; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004967:Estrogens; D009842:Oligopeptides; D010455:Peptides; C047981:arginyl-glycyl-aspartic acid