ISSN:
1573-501X
Keywords:
combinatorial libraries
;
endotoxin
;
molecular recognition
;
peptide conformation
;
septic shock
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1016207717213
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