ArticleProceedings of the National Academy of Sciences of the United States of America2009
Peptides modulating conformational changes in secreted chaperones: from in silico design to preclinical proof of concept.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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
17 citing papers in PubMed, 38 citations in OpenAlex.
- The Potential of Hsp90 in Targeting Pathological Pathways in Cardiac Diseases.Journal of personalized medicine · 2021Review
- COMTOP: Protein Residue-Residue Contact Prediction through Mixed Integer Linear Optimization.Membranes · 2021Article
- Peptides to combat viral infectious diseases.Peptides · 2020Review
- Extracellular gp96 is a crucial mediator for driving immune hyperactivation and liver damage.Scientific reports · 2020Article
- RRCRank: a fusion method using rank strategy for residue-residue contact prediction.BMC bioinformatics · 2017Article
- Gp96 Peptide Antagonist gp96-II Confers Therapeutic Effects in Murine Intestinal Inflammation.Frontiers in immunology · 2017Article
- Experimental Anti-Inflammatory Drug Semapimod Inhibits TLR Signaling by Targeting the TLR Chaperone gp96.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Protein Residue Contacts and Prediction Methods.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Article
- Expression of heat-shock protein gp96 in gallbladder cancer and its prognostic clinical significance.International journal of clinical and experimental pathology · 2015Article
- Human α1-Antitrypsin Binds to Heat-Shock Protein gp96 and Protects from Endogenous gp96-Mediated Injury In vivo.Frontiers in immunology · 2013Article
- A study and benchmark of DNcon: a method for protein residue-residue contact prediction using deep networks.BMC bioinformatics · 2013Article
- Predicting protein residue-residue contacts using deep networks and boosting.Bioinformatics (Oxford, England) · 2012Article
- Chaperone gp96-independent inhibition of endotoxin response by chaperone-based peptide inhibitors.The Journal of biological chemistry · 2012Article
- A novel angiopoietin-derived peptide displays anti-angiogenic activity and inhibits tumour-induced and retinal neovascularization.British journal of pharmacology · 2012Article
- The molecular chaperone gp96/GRP94 interacts with Toll-like receptors and integrins via its C-terminal hydrophobic domain.The Journal of biological chemistry · 2012Article
- A conformation ensemble approach to protein residue-residue contact.BMC structural biology · 2011Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blocking conformational changes in biologically active proteins holds therapeutic promise. Inspired by the susceptibility of viral entry to inhibition by synthetic peptides that block the formation of helix-helix interactions in viral envelope proteins, we developed a computational approach for predicting interacting helices. Using this approach, which combines correlated mutations analysis and Fourier transform, we designed peptides that target gp96 and clusterin, 2 secreted chaperones known to shift between inactive and active conformations. In human blood mononuclear cells, the gp96-derived peptide inhibited the production of TNFalpha, IL-1beta, IL-6, and IL-8 induced by endotoxin by >80%. When injected into mice, the peptide reduced circulating levels of endotoxin-induced TNFalpha, IL-6, and IFNgamma by >50%. The clusterin-derived peptide arrested proliferation of several neoplastic cell lines, and significantly enhanced the cytostatic activity of taxol in vitro and in a xenograft model of lung cancer. Also, the predicted mode of action of the active peptides was experimentally verified. Both peptides bound to their parent proteins, and their biological activity was abolished in the presence of the peptides corresponding to the counterpart helices. These data demonstrate a previously uncharacterized method for rational design of protein antagonists.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.