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Design and facile solid‐phase synthesis of peptide‐based LPS‐inhibitors containing PEG‐like functionalities
Author(s) -
MasMoruno Carlos,
Cascales Laura,
Mora Puig,
Cruz Luis J.,
PérezPayá Enrique,
Albericio Fernando
Publication year - 2009
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21285
Subject(s) - peptide , chemistry , preprint , combinatorial chemistry , peptide synthesis , peg ratio , septic shock , sepsis , biochemistry , medicine , computer science , immunology , finance , world wide web , economics
LPS release from Gram‐negative bacteria can result in sepsis, a serious systemic inflammatory response to infection that can lead to septic shock and multiple organ failure. Thus, easy‐to‐synthesize, effective, and safe LPS‐inhibitors are required to develop new agents for the treatment of sepsis. On the basis of the chemical features of the toxic part of LPS, lipid A, here we present peptide‐based LPS‐neutralizers that can be readily obtained using solid‐phase methodologies. The presence of PEG‐like moieties yielded the most active compounds, thereby indicating that these functionalities may be of great value in the design of new inhibitors. In this regard, the substitution of several amino acids by PEG‐like chains in a previously reported cyclic anti‐LPS peptide (the peptide RLKWc ) rendered a new derivative that retained the activity of the original peptide. We foresee that this strategy could be successfully applied to other LPS‐neutralizing peptides. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 508–517, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com