Sequence and structural diversity in endotoxin-binding dodecapeptides.
For the study of sequence or structure requirement of short peptides for endotoxin binding, and to search for potential endotoxin antagonists, biopanning was carried out on a phage-displayed random dodecapeptide library against immobilized lipopolysaccharide (LPS) or lipid A (LA), the core toxic portion of LPS. Specific binding of selected phage-displayed peptides to LPS/LA was confirmed by surface plasmon resonance (SPR) analysis. These peptides are rich in basic and hydrophobic amino acids, especially histidine, proline and tryptophan, highlighting apparent amphiphilicity and bacterial membrane activity. These dodecapeptide sequences have no predictable secondary structure in solution, indicating the importance of a random structure before their interaction with LPS/LA. Sequence alignment reveals various potential secondary structures with these selected peptides, which contain specific signature motifs such as b(p)hb(p)hb(p), bbbb, hhhh (b-basic, p-polar, h-hydrophobic residue), capable of binding LPS/LA. However, none of these peptides exhibit a significant calculated structural amphiphilicity while assuming a secondary structure. This study suggests that for these short dodecapeptides to bind LPS/LA, the potential for their structural adaptation is more important than an amphipathic structure.
Zhu
Yong
Y
Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
Ho
Bow
B
Ding
Jeak Ling
JL
D000595:Amino Acid Sequence; D001435:Bacteriophages; D016384:Consensus Sequence; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008050:Lipid A / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry; D020411:Oligonucleotide Array Sequence Analysis; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D009994:Osmolar Concentration; D016415:Sequence Alignment; D020349:Surface Plasmon Resonance
D004731:Endotoxins; D008050:Lipid A; D008070:Lipopolysaccharides; D009842:Oligopeptides