An engineered cyclic peptide alleviates symptoms of inflammation in a murine model of inflammatory bowel disease.
J Biol Chem
; 292(24): 10288-10294, 2017 06 16.
Article
em En
| MEDLINE
| ID: mdl-28473469
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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Peptídeos Cíclicos
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Fármacos Gastrointestinais
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Colite Ulcerativa
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Modelos Moleculares
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Anti-Inflamatórios não Esteroides
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Colo
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Modelos Animais de Doenças
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Austrália