ArticleACS chemical biology2011
Synthesis and activity of thioether-containing analogues of the complement inhibitor compstatin.
Article in ACS chemical biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 84 citations in OpenAlex.
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- StrEAMM-Thioether: Efficient Structure Prediction for Thioether-Linked Cyclic Peptides.The journal of physical chemistry. B · 2026Article
- From Diarylsulfides to Diarylamines: New Ebola Virus Entry Inhibitors with Improved Metabolic Stability.Journal of medicinal chemistry · 2025Article
- Affinity selection-mass spectrometry with linearizable macrocyclic peptide libraries.Science advances · 2025Article
- Synthesis of Novel Indole Schiff Base Compounds and Their Antifungal Activities.Molecules (Basel, Switzerland) · 2022Article
- Late-Stage Functionalisation of Peptides on the Solid Phase by an Iodination-Substitution Approach.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Compstatins: the dawn of clinical C3-targeted complement inhibition.Trends in pharmacological sciences · 2022Review
- Effect of Disulfide Cyclization of Ultrashort Cationic Lipopeptides on Antimicrobial Activity and Cytotoxicity.International journal of molecular sciences · 2020Article
- α-Conotoxin Peptidomimetics: Probing the Minimal Binding Motif for Effective Analgesia.Toxins · 2020Review
- Genome mining, isolation, chemical synthesis and biological evaluation of a novel lanthipeptide, tikitericin, from the extremophilic microorganismChemical science · 2018Article
- 1,2,3-Triazole Rings as a Disulfide Bond Mimetic in Chimeric AGRP-Melanocortin Peptides: Design, Synthesis, and Functional Characterization.ACS chemical neuroscience · 2018Article
- The Role of Disulfide Bond Replacements in Analogues of the Tarantula Toxin ProTx-II and Their Effects on Inhibition of the Voltage-Gated Sodium Ion Channel NaJournal of the American Chemical Society · 2017Article
- Design and Evolution of a Macrocyclic Peptide Inhibitor of the Sonic Hedgehog/Patched Interaction.Journal of the American Chemical Society · 2017Article
- Method development and validation for the quantitation of the complement inhibitor Cp40 in human and cynomolgus monkey plasma by UPLC-ESI-MS.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2017Article
- Site-Selective Disulfide Modification of Proteins: Expanding Diversity beyond the Proteome.Chemistry (Weinheim an der Bergstrasse, Germany) · 2016Review
- Phosphoserine Lyase Deoxyribozymes: DNA-Catalyzed Formation of Dehydroalanine Residues in Peptides.Journal of the American Chemical Society · 2015Article
- Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention.European journal of clinical investigation · 2015Review
- New compstatin peptides containing N-terminal extensions and non-natural amino acids exhibit potent complement inhibition and improved solubility characteristics.Journal of medicinal chemistry · 2015Article
- Strategies for the development of conotoxins as new therapeutic leads.Marine drugs · 2013Review
- New analogs of the clinical complement inhibitor compstatin with subnanomolar affinity and enhanced pharmacokinetic properties.Immunobiology · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Disulfide bonds are essential for the structural stability and biological activity of many bioactive peptides. However, these bonds are labile to reducing agents, which can limit the therapeutic utility of such peptides. Substitution of a disulfide bond with a reduction-resistant cystathionine bridge is an attractive means of improving stability while imposing minimal structural perturbation to the peptide. We have applied this approach to the therapeutic complement inhibitor compstatin, a disulfide-containing peptide currently in clinical trials for age-related macular degeneration, in an effort to maintain its potent activity while improving its biological stability. Thioether-containing compstatin analogues were produced via solid-phase peptide synthesis utilizing orthogonally protected cystathionine amino acid building blocks and solid-supported peptide cyclization. Overall, the affinity of these analogues for their biological target and potent inhibition of complement activation were largely maintained when compared to those of the parent disulfide-containing peptides. Thus, the improved stability to reduction conferred by the thioether bond makes this new class of compstatin peptides a promising alternative for therapeutic applications. Additionally, the versatility of this synthesis allows for exploration of disulfide-to-thioether substitution in a variety of other therapeutic peptides.
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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.