Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Alkaline Phosphatase / blood
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Animals
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Blood Coagulation / drug effects
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Calcium / blood
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Calcium / metabolism
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Endometrial Hyperplasia / chemically induced
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Estradiol / chemistry*
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Female
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Femur / drug effects
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Femur / metabolism
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Mice
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Mice, Inbred ICR
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Minerals / metabolism
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Models, Molecular
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Molecular Conformation
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Oligopeptides / administration & dosage
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Oligopeptides / adverse effects
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Oligopeptides / chemical synthesis*
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Oligopeptides / pharmacology*
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Organ Size / drug effects
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Osteoporosis / blood
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Osteoporosis / drug therapy*
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Osteoporosis / metabolism
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Phosphorus / metabolism
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Quantitative Structure-Activity Relationship*
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Reference Standards
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Thromboembolism / chemically induced
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Uterus / drug effects
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Uterus / pathology
Substances
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Minerals
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Oligopeptides
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Phosphorus
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Estradiol
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arginyl-glycyl-aspartic acid
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Alkaline Phosphatase
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Calcium