ArticleThe protein journal2019
Grafting, Stripping and Stapling of Helical Peptides from the Dimerization Interface of ONFH-Related Bone Morphogenetic Protein-2.
Article in The protein journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed, 5 citations in OpenAlex.
- Rational design of type-IA receptor-derived cyclic peptides to target human bone morphogenic protein 2.Journal of biosciences · 2019Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Transforming growth factor-β/bone morphogenetic protein (TGF-β/BMP) signaling plays a fundamental role in embryonic skeletal development and postnatal bone homeostasis. The signaling pivot protein BMP-2 belongs to the TGF-β superfamily and has been implicated in the pathogenesis of osteonecrosis of femoral head (ONFH). The biologically functional BMP-2 is a homodimer that has two tightly packed cores at its dimerization interface; each core is defined by the intermolecular interaction between a helical arm from one monomer and a hydrophobic pocket from another monomer. Inhibition and disruption of BMP-2 dimerization have been recognized as an attractive therapeutic strategy against ONFH. Here, we investigate the self-binding behavior of helical arm-derived peptides to the BMP-2 dimerization interface. The native BMP-2 helical arm and its several grafted versions from BMP-4, BMP-6 and BMP-7 are stripped from the intact dimerization interface to generate a number of isolated helical peptides. Computational simulations demonstrate that the stripping does not substantially influence the direct intermolecular interaction between BMP-2 monomer and these helical peptides or desolvation effect upon the interaction. However, the C-terminus of stripped peptides is found to have an intrinsic disorder and large flexibility in the isolated state, which would impair the rebinding of stripped peptides to BMP-2. Next, we rationally design a hydrocarbon bridge across the C-terminal residues 65 and 69 of helical peptides, which can effectively constrain peptide conformational flexibility in the isolated state, thus considerably promoting the binding potency of stripped helical peptides. Circular dichroism (CD) spectroscopy reveals that the peptide helicity increases from 51.8 to 67.9% upon hydrocarbon stapling. Fluorescence polarization assays substantiate that, as designed, the stapling can convert these helical peptides from weak binders to moderate or good binders of BMP-2 protein; their K
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Registered trials
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