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

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.