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Identification of peptides that neutralize bacterial endotoxins using β-hairpin conformationally restricted libraries

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Abstract

Bacterial endotoxins are the major mediator of septic shock; therefore, endotoxin-neutralizing molecules could have biomedicalapplications. The septic shock cascade relies in a series of molecular recognition processes. The large contact-surface described for the interacting macromolecules, in most cases, prevents the identification of small molecules that could modulate such recognition events. Here we report on a β-hairpin conformationally restricted combinatorial librarythat has been generated and screened towards the identification of new peptides that neutralize bacterial endotoxins. Starting with a de novo designed linear peptide that shows a β-hairpin structure population of around 30%, (Ramirez-Alvarado, M., Blanco, F. J. and Serrano, L. Nat. Struc. Biol., 7, 604–612 (1996)), we selected four positions tobuild up a combinatorial library of 204 sequences. Deconvolution of the library reduced such a sequence complexity to 8 defined sequences. The newly identified peptides have a biological activity equivalent to that reported for peptides derived from natural endotoxin-binding proteins.

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Author notes

  1. Herminia González-Navarro

    Present address: Molecular Disease Branch, NHLBI/NIH, Bldg 10, 7N108, 9000 Rockville Pike, Bethesda, Maryland, 20892, U.S.A.

Authors and Affiliations

  1. Dept. Bioquímica i Biologia Molecular, Universitat de València, E-46100, Burjassot, València, Spain

    Herminia González-Navarro, Puig Mora, Mayte Pastor, Ismael Mingarro & Enrique Pérez-Payá

  2. European Molecular Biology Laboratory, Structures and Biocomputing, Meyerhofstrasse 1, D-69012, Heidelberg, Germany

    Luis Serrano

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  1. Herminia González-Navarro
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Correspondence to Enrique Pérez-Payá.

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González-Navarro, H., Mora, P., Pastor, M. et al. Identification of peptides that neutralize bacterial endotoxins using β-hairpin conformationally restricted libraries. Mol Divers 5, 117–126 (2000). https://doi.org/10.1023/A:1016207717213

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