Title
Oxpholipin 11D: An Anti-Inflammatory Peptide That Binds Cholesterol and Oxidized Phospholipids
Author
Piotr Ruchala, Mohamad Navab, Chun-Ling Jung, Susan Hama-Levy, Ewa D. Micewicz, Hai Luong, Jonathan E. Reyles, Shantanu Sharma, Alan J. Waring, Alan M. Fogelman, Robert I. Lehrer
Year
2010
Journal
PLoS ONE
Abstract
Many Gram-positive bacteria produce pore-forming exotoxins that contain a highly conserved, 12-residue domain (ECTGLAWEWWRT) that binds cholesterol. This domain is usually flanked N-terminally by arginine and C-terminally by valine. We used this 14-residue sequence as a template to create a small library of peptides that bind cholesterol and other lipids. Several of these peptides manifested anti-inflammatory properties in a predictive in vitro monocyte chemotactic assay, and some also diminished the pro-inflammatory effects of low-density lipoprotein in apoE-deficient mice. The most potent analog, Oxpholipin-11D (OxP-11D), contained D-amino acids exclusively and was identical to the 14-residue design template except that diphenylalanine replaced cysteine-3. In surface plasmon resonance binding studies, OxP-11D bound oxidized (phospho)lipids and sterols in much the same manner as D-4F, a widely studied cardioprotective apoA-I-mimetic peptide with anti-inflammatory properties. In contrast to D-4F, which adopts a stable α-helical structure in solution, the OxP-11D structure was flexible and contained multiple turn-like features. Given the substantial evidence that oxidized phospholipids are pro-inflammatory in vivo, OxP-11D and other Oxpholipins may have therapeutic potential.
Instrument
J-715
Keywords
Circular dichroism, Secondary structure, Chemical stability, Biochemistry