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Peptides. 2010 Oct;31(10):1853-9. doi: 10.1016/j.peptides.2010.07.004. Epub 2010 Jul 17.

Lipopolysaccharide (LPS) detoxification of analogue peptides derived from limulus anti-LPS factor.

Author information

1
Department of General Surgery, General Hospital of Chengdu Military Command, Chengdu 610083, China.

Abstract

Lipopolysaccharide (LPS) plays a critical role in the pathogenesis of sepsis due to gram-negative bacterial infections. Therefore, LPS-neutralizing molecules could have important clinical applications. Our previous work showed, CLP19, an analogue peptide derived from limulus anti-LPS factor (LALF), possessed the capacity to neutralize LPS and thereby inhibit the LPS-induced responses. However, potential cytotoxicity of CLP19 was also found, especially when added to human red blood cells. Accordingly we further developed two peptides (designated as CLP19-1 and CLP19-2) by single- and double-point amino acid substitution of CLP19, respectively, in order to reduce its toxicity and meanwhile retain the anti-LPS activity. In this study, the LPS-detoxifying effectiveness of these peptides was evaluated both in vitro and in vivo. CLP19-1 was found to dose-dependently neutralize LPS in vitro, with significantly lower hemolysis of red blood cells as compared with CLP19. Further in vivo tests verified that CLP19-1 exerted significant protective effects on mice against LPS, characterized by significantly improved survival, decreasing of tumor necrosis factor alpha (TNF-α) serum level and alleviation of tissue injury. Our work indicates that CLP19-1 is worthy of further study as potential anti-LPS agents for the management of sepsis.

PMID:
20624438
DOI:
10.1016/j.peptides.2010.07.004
[Indexed for MEDLINE]

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