Development of three-component conjugates: to get nano-globes with porous surfaces, high in vivo anti-osteoporosis activity and minimal side effects

Guifeng Kang; Yuji Wang; Jiawang Liu; Jianhui Wu; Ming Zhao; Guochun Li; Ning Li; Li Peng; Xiaoyi Zhang; Li Li; Nathan Mair; Shiqi Peng

doi:10.1039/C2JM34370C

Development of three-component conjugates: to get nano-globes with porous surfaces, high in vivo anti-osteoporosis activity and minimal side effects†

Guifeng Kang,‡^a Yuji Wang,‡^a Jiawang Liu,^a Jianhui Wu,^a Ming Zhao,*^a Guochun Li,^a Ning Li,^a Li Peng,^a Xiaoyi Zhang,^a Li Li,^a Nathan Mair^a and Shiqi Peng*^a

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* Corresponding authors

^a College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, P.R.China
E-mail: sqpeng@mail.bjmu.edu.cn, mingzhao@mail.bjmu.edu.cn
Fax: +86-10-8391-1528
Tel: +86-10-8391-1528

Abstract

Three novel three-component conjugates of a succinyl spacer, a pharmacophore of 17β-amino-11α-hydroxyl-androst-1,4-diene-3-one, and a targeting sequence of RGD-tetrapeptide (peptide Arg-Gly-Asp-AA) were designed, synthesized, and evaluated. This paper presents evidence that inserting a succinyl functional group into the pharmacophore and the targeting sequence improves the oral anti-osteoporosis activities in mouse glucocorticoid model of secondary osteoporosis, which were reflected by dry weight, ash weight, Ca²⁺ and bone mineral content of the femur of examined mice. These novel conjugates have no side effects on estrogen, and form nano-globes with a porous surface. This paper emphasizes that the hydrogen bond between the carbonyl group of the succinyl group and the carboxylic group of the C-terminal amino acid residue of RGD-tetrapeptides is the key to forming pores on the surface of the nano-globes of these novel conjugates.

Journal of Materials Chemistry

Development of three-component conjugates: to get nano-globes with porous surfaces, high in vivo anti-osteoporosis activity and minimal side effects†

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Development of three-component conjugates: to get nano-globes with porous surfaces, high in vivo anti-osteoporosis activity and minimal side effects

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