ArticleBioorganic & medicinal chemistry letters2012
Developing potent backbone cyclic peptides bearing the shared epitope sequence as rheumatoid arthritis drug-leads.
Article in Bioorganic & medicinal chemistry letters, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Anti-Inflammatory Effects of Clarstatin, a Shared-Epitope-Antagonistic Cyclic Peptide, on Experimental Autoimmune Uveitis in Mice.Investigative ophthalmology & visual science · 2025Article
- Development of Clarstatin, a Novel Drug Lead for the Therapy of Autoimmune Uveitis.Pharmaceutics · 2024Article
- HLA-G and the MHC Cusp Theory.Frontiers in immunology · 2022Review
- Current research status of HLA in immune-related diseases.Immunity, inflammation and disease · 2021Review
- Shared epitope-aryl hydrocarbon receptor crosstalk underlies the mechanism of gene-environment interaction in autoimmune arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Cyclic Peptides that Govern Signal Transduction Pathways: From Prokaryotes to Multi-Cellular Organisms.Current topics in medicinal chemistry · 2018Review
- Conversion of Protein Active Regions into Peptidomimetic Therapeutic Leads Using Backbone Cyclization and Cycloscan - How to Do it Yourself!Current topics in medicinal chemistry · 2018Review
- Human Leukocyte Antigen-Disease Associations in Rheumatoid Arthritis.Rheumatic diseases clinics of North America · 2017Review
- Spontaneous destructive periodontitis and skeletal bone damage in transgenic mice carrying a human shared epitope-codingRMD open · 2016Article
- Shared epitope-antagonistic ligands: a new therapeutic strategy in mice with erosive arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2015Article
- The quest for better understanding of HLA-disease association: scenes from a road less travelled by.Discovery medicine · 2013Review
- A small shared epitope-mimetic compound potently accelerates osteoclast-mediated bone damage in autoimmune arthritis.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- An HLA-DRB1-coded signal transduction ligand facilitates inflammatory arthritis: a new mechanism of autoimmunity.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Rheumatoid arthritis (RA) is a common human leukocyte antigen-associated disease. Most RA patients have a five-residue sequence motif called the shared epitope (SE) in the DRβ-chain of the HLA-DRB1 protein. The SE was found to activate nitric oxide (NO) production, suggesting a possible mechanism for RA development. The native conformation of the SE is presumed to be an α-helix, thus using cyclic peptides to stabilize this conformation may produce a potent SE mimetic which will have drug-like properties. We present the development of a backbone cyclic SE mimetic that activates NO production in the low nM range. Circular dichroism analysis revealed a conformational change from for the parent linear peptides to the cyclic analogs. The most active cyclic analog is completely stable towards trypsin/chymotrypsin degradation while the linear 15-mer analogs completely degraded within 30 min. The outcome of this study is a potent cyclic peptide with drug-like properties that can be used as a template for drug development.
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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.