Add time:07/22/2019         Source:sciencedirect.com

Osteoporotic fracture is a significant public health problem, resulting in fractures in >50% of women and in almost one third of men age 65 and older. Most of the existing therapies act by slowing bone loss, through inhibiting the action of bone resorbing cells. However, more substantial reductions of fracture numbers will only result from treatments that can rebuild bone. Our own animal studies demonstrated the anabolic potential of the small but unstable octapeptide fragment of amylin-(1–37), namely amylin-(1–8) containing one disulfide bridge (Cys/2 and Cys/7) [Am. J. Physiol. Endocrinol. Metab. 2000, 279, E730]. Herein, we describe the synthesis of amylin-(1–8) octapeptide and seven analogues thereof wherein the disulfide bridge is modified either via insertion of different linkers or bridges of a different nature in order to improve the stability and/or bone anabolic activity of the parent peptide. The peptide analogues were screened for proliferative activity in primary foetal rat bone-forming cells or osteoblasts at physiological concentrations. One such analogue showed promising biological activity.

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