Development of cyclic peptides with potent in vivo osteogenic activity through RaPID-based affinity maturation
Year: 2020
Type: article
Abstract: Significance Osteoporosis affects over 75 million people globally, and this number is increasing with global median age. Therefore, the development of therapeutics with novel mechanisms of action is of high importance. Inhibition of the PlexinB1-Semaphorin4D interaction on osteoblasts has been shown to be a potential target for developing osteoanabolic modalities. Here, using a novel affinity maturation approach for cyclic peptides, we were able to develop cyclic peptide that tightly binds human and mouse PlexinB1 and inhibits its interaction with Semaphorin4D. Chemical dimerization of this peptide resulted in further increases in activity and demonstrated complete rescue of bone loss in an osteoporosis mouse model.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: Elucidation of the bone remodeling governing bone homeostasis and establishment of innovative treatment strategies, Challenges to the remaining issues of therapeutically valuable pseudo-natural peptides and products, Novel design of AAV capsid by LassoGraft Technology, Structural elucidation of Wnt signaling mechanism using unique chemical tools
OpenAlex ID: W3110390608