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

Peer Reviewed