Properties of apolipoprotein E derived peptide modulate their lipid-binding capacity and influence their anti-inflammatory function.
Apolipoprotein-derived peptides are promising candidates for the treatment of various inflammatory conditions. The beneficial effects of these peptides are based on multiple mechanisms; prominent among them being high-affinity binding to pro-inflammatory oxidized phospholipids (Ox-PLs) and facilitating their sequestration/metabolism/clearance in the body. This indicates that peptides which can bind exclusively to Ox-PLs without recognizing normal, non-oxidized phospholipids (non-Ox-PLs) will be more potent anti-inflammatory agent than that of the peptides that bind to both Ox-PLs and non-Ox-PLs. In order to develop such Ox-PL-specific peptides, the knowledge about the properties (molecular determinants) of peptides that govern their Ox-PL preference is a must. In this study we have synthesized eleven peptides corresponding to the conserved regions of human apolipoprotein E and compared their biochemical properties, lipid-binding specificities, and anti-inflammatory properties. Our results show that these peptides exhibit considerably different specificities towards non-Ox-PL and different species of Ox-PLs. Some of these peptides bind exclusively to the Ox-PLs and inhibit the pro-inflammatory function of Ox-PLs in human blood. Biochemical characterization revealed that the peptides possess substantially different properties. Our results suggest that physicochemical properties of peptides play an important role in their lipid-binding specificity.
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India.
Sunil A
SA
Nankar
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India. Electronic address: apande@niper.ac.in.
Abhay H
AH
Pande
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism; D001057:Apolipoproteins E / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002942:Circular Dichroism; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
D000893:Anti-Inflammatory Agents; D001057:Apolipoproteins E; D010455:Peptides; D010743:Phospholipids
Apolipoprotein-derived peptide; Circular dichroism; ELISA; Inflammation; Ox-PAPC; qRT-PCR