Properties of apolipoprotein E derived peptide modulate their lipid-binding capacity and influence their anti-inflammatory function.
| Autor: | Nankar SA; Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India., Pande AH; 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. |
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| Jazyk: | angličtina |
| Zdroj: | Biochimica et biophysica acta [Biochim Biophys Acta] 2014 Apr 04; Vol. 1841 (4), pp. 620-9. Date of Electronic Publication: 2014 Jan 31. |
| DOI: | 10.1016/j.bbalip.2014.01.006 |
| Abstrakt: | 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. (Copyright © 2014 Elsevier B.V. All rights reserved.) |
| Databáze: | MEDLINE |
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