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Design of a minimized cyclic tetrapeptide that neutralizes bacterial endotoxins
Author(s) -
Mora Puig,
MasMoruno Carlos,
Tamborero Silvia,
Cruz Luis J.,
PÉrezPayÁ Enrique,
Albericio Fernando
Publication year - 2006
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.755
Subject(s) - tetrapeptide , peptide , peptide sequence , amino acid , biological activity , cyclic peptide , chemistry , sequence (biology) , small molecule , biochemistry , amino acid residue , combinatorial chemistry , computational biology , in vitro , biology , gene
Septic shock is a leading cause of mortality in intensive care patients, and no specific drugs are as yet available for its treatment. Therefore, new leads are required in order to increase the number of active molecules that may develop into efficacious and safe LPS‐neutralizing molecules during pre‐clinical stages. We used peptides, derived from the binding regions of known LPS‐binding proteins, as scaffolds to introduce modifications at the amino acid level. Structure–activity relationship studies have shown that these modifications generate highly active peptides. Thus, from a bioactive peptide with an initial 16 amino acid residues, a tetrapeptide sequence was determined. After inserting this sequence in a Cys cyclic peptide, it showed the same biological activity as the parent peptide. This sequence could provide the basis for the design of small molecules with LPS‐binding properties. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd.