5VFW

An engineered cyclic peptide alleviates symptoms of inflammation in a murine model of inflammatory bowel disease


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: target function 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

An engineered cyclic peptide alleviates symptoms of inflammation in a murine model of inflammatory bowel disease.

Cobos Caceres, C.Bansal, P.S.Navarro, S.Wilson, D.Don, L.Giacomin, P.Loukas, A.Daly, N.L.

(2017) J Biol Chem 292: 10288-10294

  • DOI: https://doi.org/10.1074/jbc.M117.779215
  • Primary Citation of Related Structures:  
    5VAV, 5VFW

  • PubMed Abstract: 

    Inflammatory bowel diseases (IBDs) are a set of complex and debilitating diseases for which there is no satisfactory treatment. Recent studies have shown that small peptides show promise for reducing inflammation in models of IBD. However, these small peptides are likely to be unstable and rapidly cleared from the circulation, and therefore, if not modified for better stability, represent non-viable drug leads. We hypothesized that improving the stability of these peptides by grafting them into a stable cyclic peptide scaffold may enhance their therapeutic potential. Using this approach, we have designed a novel cyclic peptide that comprises a small bioactive peptide from the annexin A1 protein grafted into a sunflower trypsin inhibitor cyclic scaffold. We used native chemical ligation to synthesize the grafted cyclic peptide. This engineered cyclic peptide maintained the overall fold of the naturally occurring cyclic peptide, was more effective at reducing inflammation in a mouse model of acute colitis than the bioactive peptide alone, and showed enhanced stability in human serum. Our findings suggest that the use of cyclic peptides as structural backbones offers a promising approach for the treatment of IBD and potentially other chronic inflammatory conditions.


  • Organizational Affiliation

    From the Centre for Biodiscovery and Molecular Development of Therapeutics, AITHM, James Cook University, Cairns, Queensland 4870, Australia.


Macromolecules

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Annexin A125Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P04083 (Homo sapiens)
Explore P04083 
Go to UniProtKB:  P04083
PHAROS:  P04083
GTEx:  ENSG00000135046 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04083
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: target function 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-05-10
    Type: Initial release
  • Version 1.1: 2017-05-24
    Changes: Database references
  • Version 1.2: 2017-06-28
    Changes: Database references
  • Version 1.3: 2023-06-14
    Changes: Data collection, Database references, Other
  • Version 1.4: 2024-05-15
    Changes: Data collection, Database references