Development of cyclic peptides with potent in vivo osteogenic activity through RaPID-based affinity maturation.
PlexinB1
cyclic peptides
in vitro selection
osteoporosis
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
08 12 2020
08 12 2020
Historique:
pubmed:
25
11
2020
medline:
22
1
2021
entrez:
24
11
2020
Statut:
ppublish
Résumé
Osteoporosis is caused by a disequilibrium between bone resorption and bone formation. Therapeutics for osteoporosis can be divided into antiresorptives that suppress bone resorption and anabolics which increase bone formation. Currently, the only anabolic treatment options are parathyroid hormone mimetics or an anti-sclerostin monoclonal antibody. With the current global increases in demographics at risk for osteoporosis, development of therapeutics that elicit anabolic activity through alternative mechanisms is imperative. Blockade of the PlexinB1 and Semaphorin4D interaction on osteoblasts has been shown to be a promising mechanism to increase bone formation. Here we report the discovery of cyclic peptides by a novel RaPID (Random nonstandard Peptides Integrated Discovery) system-based affinity maturation methodology that generated the peptide PB1m6A9 which binds with high affinity to both human and mouse PlexinB1. The chemically dimerized peptide, PB1
Identifiants
pubmed: 33229551
pii: 2012266117
doi: 10.1073/pnas.2012266117
pmc: PMC7733813
doi:
Substances chimiques
Peptide Library
0
Peptides, Cyclic
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
31070-31077Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Competing interest statement: N.K.B., Y.M., J.T., and H.S. are inventors of a patent application titled “Plexin Binding Regulator” (US20190247457A1). All other authors declare no competing interests.
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