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Rational design of stapled peptides targeting phosphorylated GSK3β for regulating osteoclast differentiation.

ABSTRACT: Glycogen synthase kinase-3β (GSK-3β), has been reported to show essential roles in osteoclast differentiation. Modeled after FRATtide, a peptide derived from a GSK-3 binding protein, here we designed and synthesized a series of stapled peptides targeting phosphorylated GSK3β, and evaluated the corresponding biological activities. The results indicated that stapled peptides with better helical contents and proteolytic stability than the linear ones showed improved biological activity in inhibiting osteoclast differentiation. Among them, FRC-2 and FRN-2 showed promising prospects for treating osteoporosis.

SUBMITTER: Liu T

PROVIDER: S-EPMC9049898 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Rational design of stapled peptides targeting phosphorylated GSK3β for regulating osteoclast differentiation.

Liu Tairong T Cong Wei W Ye Lei L Xu Xike X Liao Xiufei X Xie Gang G Cheng Zhaoxi Z Hu Honggang H Li Xiang X Liao Hongli H

RSC advances 20200224 13

Glycogen synthase kinase-3β (GSK-3β), has been reported to show essential roles in osteoclast differentiation. Modeled after FRATtide, a peptide derived from a GSK-3 binding protein, here we designed and synthesized a series of stapled peptides targeting phosphorylated GSK3β, and evaluated the corresponding biological activities. The results indicated that stapled peptides with better helical contents and proteolytic stability than the linear ones showed improved biological activity in inhibitin ...[more]

PMID: 35492160

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