arginyl-glycyl-aspartyl-phenylalanine and Thromboembolism

To enhance the potency, reduce the side effects and improve oral property of estradiol in estrogen replacement therapy (ERT), 6 novel estradiol-RGD octapeptide conjugates have been prepared. In an ovariectomized mouse osteoporotic model, at an oral dosage of 110.3 nmol/kg per day, their anti-osteoporosis activity was significantly higher than that of estradiol and estradiol-RGD tetrapeptide conjugates, and their risks of thrombogenesis and endometrial hyperplasia were significantly lower than that of estradiol and estradiol-RGD tetrapeptide conjugates. Using QSAR module of Cerius2, the 3D QSAR was performed for both femur weights and femur ash weights of estradiol-RGD peptide conjugates receiving mice. The r(2) of the 3D QSAR equations up to 0.995 and 0.988 indicates that they are capable of predicting a comparatively exact anti-osteoporosis activity for a conjugate.

Topics: Administration, Oral; Alkaline Phosphatase; Animals; Blood Coagulation; Calcium; Endometrial Hyperplasia; Estradiol; Female; Femur; Mice; Mice, Inbred ICR; Minerals; Models, Molecular; Molecular Conformation; Oligopeptides; Organ Size; Osteoporosis; Phosphorus; Quantitative Structure-Activity Relationship; Reference Standards; Thromboembolism; Uterus