Fig. 7
The multiple effects of TCPs. TCPs exert anti-inflammatory effects and protect from endotoxic shock and bacterial sepsis in experimental animal models5,7,8,22. Binding of the TCP HVF18 to LPS leads to a structural transition, wherein the peptide forms a C-shaped structure comprising a C-terminal helix, and serves in LPS scavenging and bacterial cell neutralisation. TCPs not only interact with bacteria and LPS, but also directly with monocytes/macrophages, leading to interference with TLR4 dimerization20 as well as to CD14 (Kd ~μM levels) on monocytes and macrophages, and may be subsequently internalised. This is proposed to competitively block CD14–LPS interaction, and/or to prevent transfer of LPS to the TLR4/MD-2 complex, thus interfering with TLR4 dimerisation and downstream inflammatory responses47. This effect is abrogated in a scrambled, amphipathic TCP sequence, which retains affinity for LPS but demonstrates no anti-endotoxic activity
