Improved anti-osteoporosis potency and reduced endometrial membrane hyperplasia during hormone replacement therapy with estrogen-RGD peptide conjugates.
To improve the specificity and potency of estrogen replacement therapy therapeutics while also minimizing the side effects such as bone resorption and thickening of the uterine wall, a series of novel estrogen-derived conjugates estradiol-3-RGD, estradiol-17-RGD, and estrone-3-RGD peptides have been prepared. In a mouse model, intraperitoneal (i.p.) administration of these estrogen-RGD peptide conjugates resulted in decreased serum concentrations of calcium and alkaline phosphatase, as well as increased levels of calcium, phosphorus, and minerals in the mouse femur. Furthermore, the anti-osteoporosis action of these conjugates followed a dose-dependent manner and was accompanied with no observable effects on endometrial cell hyperplasia. In addition to all of these compounds exhibiting biological activity when administered by the i.p. route, we were particularly pleased to note that the estradiol-3-RGD and estradiol-17-RGD conjugates were both orally active.
Xiong
Yu
Y
College of Pharmaceutical Sciences, Peking University, Beijing 100083, People's Republic of China.
Zhao
Ming
M
Wang
Chao
C
Chang
Heng Wei
HW
Peng
Shiqi
S
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D002118:Calcium / Q000097:blood; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006965:Hyperplasia; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage* / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy
D004967:Estrogens; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D000469:Alkaline Phosphatase; D002118:Calcium