ArticleACS chemical biology2016
Constrained Cyclic Peptides as Immunomodulatory Inhibitors of the CD2:CD58 Protein-Protein Interaction.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Design of aptamer peptides for immunomodulation.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Drug Discovery Strategies for Kallikrein-Related Peptidases.International journal of molecular sciences · 2025Review
- Stabilized cyclic peptides as modulators of protein-protein interactions: promising strategies and biological evaluation.RSC medicinal chemistry · 2023Review
- Virtual Screening and Binding Analysis of Potential CD58 Inhibitors in Colorectal Cancer (CRC).Molecules (Basel, Switzerland) · 2023Article
- Conformationally constrained cyclic grafted peptidomimetics targeting protein-protein interactions.Peptide science (Hoboken, N.J.) · 2023Article
- Native and Engineered Cyclic Disulfide-Rich Peptides as Drug Leads.Molecules (Basel, Switzerland) · 2023Review
- Targeting protein-protein interaction for immunomodulation: A sunflower trypsin inhibitor analog peptidomimetic suppresses RA progression in CIA model.Journal of pharmacological sciences · 2022Article
- A grafted peptidomimetic for EGFR heterodimerization inhibition: Implications in NSCLC models.European journal of medicinal chemistry · 2021Article
- Modulation of co-stimulatory signal from CD2-CD58 proteins by a grafted peptide.Chemical biology & drug design · 2021Article
- CD58 Immunobiology at a Glance.Frontiers in immunology · 2021Review
- MicroRNA Variants and HLA-miRNA Interactions are Novel Rheumatoid Arthritis Susceptibility Factors.Frontiers in genetics · 2021Article
- Inhibitory Activity of a Scorpion Defensin BmKDfsin3 against Hepatitis C Virus.Antibiotics (Basel, Switzerland) · 2020Article
- Linking inhibitor motions to proteolytic stability of sunflower trypsin inhibitor-1.RSC advances · 2019Article
- Investigating cyclic peptides inhibiting CD2-CD58 interactions through molecular dynamics and molecular docking methods.Journal of computer-aided molecular design · 2018Article
- Proximity ligation assay to study protein-protein interactions of proteins on two different cells.BioTechniques · 2018Article
- Inhibitors of protein-protein interactions (PPIs): an analysis of scaffold choices and buried surface area.Current opinion in chemical biology · 2018Review
- Designing macrocyclic disulfide-rich peptides for biotechnological applications.Nature chemical biology · 2018Article
- Peptide ligands for targeting the extracellular domain of EGFR: Comparison between linear and cyclic peptides.Chemical biology & drug design · 2018Article
- Antigenic and immunogenic properties of chondrocytes. Implications for chondrocyte therapeutic transplantation and pathogenesis of inflammatory and degenerative joint diseases.Central-European journal of immunology · 2018Review
- Homo- and Heterodimerization of Proteins in Cell Signaling: Inhibition and Drug Design.Advances in protein chemistry and structural biology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The interaction between the cell-cell adhesion proteins CD2 and CD58 plays a crucial role in lymphocyte recruitment to inflammatory sites, and inhibitors of this interaction have potential as immunomodulatory drugs in autoimmune diseases. Peptides from the CD2 adhesion domain were designed to inhibit CD2:CD58 interactions. To improve the stability of the peptides, β-sheet epitopes from the CD2 region implicated in CD58 recognition were grafted into the cyclic peptide frameworks of sunflower trypsin inhibitor and rhesus theta defensin. The designed multicyclic peptides were evaluated for their ability to modulate cell-cell interactions in three different cell adhesion assays, with one candidate, SFTI-a, showing potent activity in the nanomolar range (IC50: 51 nM). This peptide also suppresses the immune responses in T cells obtained from mice that exhibit the autoimmune disease rheumatoid arthritis. SFTI-a was resistant to thermal denaturation, as judged by circular dichroism spectroscopy and mass spectrometry, and had a half-life of ∼24 h in human serum. Binding of this peptide to CD58 was predicted by molecular docking studies and experimentally confirmed by surface plasmon resonance experiments. Our results suggest that cyclic peptides from natural sources are promising scaffolds for modulating protein-protein interactions that are typically difficult to target with small-molecule compounds.
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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.