Oxidized phospholipids as potential molecular targets for antimicrobial peptides.
The effects of oxidatively modified phospholipids on the association with model biomembranes of four antimicrobial peptides (AMPs), temporin B and L, indolicidin, and LL-37(F27W) were studied by Langmuir balance and fluorescence spectroscopy. In keeping with previous reports the negatively charged phospholipid phosphatidylglycerol (PG) enhanced the intercalation of all four peptides into lipid monolayers and liposomal bilayers under low ionic strength conditions. Interestingly, similar effect was observed for 1-palmitoyl-2-(9'-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PoxnoPC), a zwitterionic oxidized phospholipid bearing an aldehyde function at the end of its truncated sn-2 acyl chain. Instead, the structurally similar 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC) containing a carboxylic moiety was less efficient in promoting the membrane association of these peptides. Physiological saline reduced the binding of the above peptides to membranes containing PG, whereas interactions with PoxnoPC were found to be insensitive to ionic strength. Notably, membrane intercalation of temporin L, the most surface active of the above peptides could be into PoxnoPC containing monolayers was strongly attenuated by methoxyamine, suggesting the importance of Schiff base formation between peptide amino groups and the lipid aldehyde function. PoxnoPC and similar aldehyde bearing oxidatively modified phospholipids could represent novel molecular targets for AMPs.
Mattila
Juha-Pekka
JP
Helsinki Biophysics and Biomembrane Group, Institute of Biomedicine/Medical Biochemistry, P.O. Box 63 (Haartmaninkatu 8), FIN-00014 University of Helsinki, Helsinki, Finland.
Sabatini
Karen
K
Kinnunen
Paavo K J
PK
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002021:Buffers; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry / Q000276:immunology; D011506:Proteins / Q000737:chemistry; D054804:Cathelicidins
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D002021:Buffers; D008081:Liposomes; D010455:Peptides; D010743:Phospholipids; D011506:Proteins; C104501:temporin; C469676:temporin L, Rana temporaria; C073143:indolicidin; D054804:Cathelicidins