Apolipoprotein-mimetic Peptides: Current and Future Prospectives.

Apolipoprotein-mimetic peptides, mimicking the biological properties of apolipoproteins, have shown beneficial properties against various diseases (central and peripheral diseases) and have emerged as potential candidates for their treatments. Progress has been made from first-generation to second-generation apolipoprotein-mimetic peptides. Understanding these peptides from the first generation to the second generation is discussed in this review. First, we discussed the structural and therapeutic potentials of first-generation apolipoprotein-mimetic peptides. Further, we discussed the development of second-generation apolipoprotein-mimetic peptides, like dual-domain and bihelical peptides the emergence of second-generation apolipoprotein-mimetic peptides as potential candidates in different preclinical and clinical studies has also been emphasized.

ApoE-Derived Peptides Attenuated Diabetes-Induced Oxidative Stress and Inflammation.

BACKGROUND: Peptides derived from the apolipoproteins (apo-mimetic peptides) have emerged as a potential candidate for the treatment of various inflammatory conditions. Our previous results have shown that peptides derived from human apolipoprotein-E interact with various pro-inflammatory lipids and inhibit their inflammatory functions in cellular assays. OBJECTIVE: In this study, two apoE-derived peptides were selected to investigate their antiinflammatory and anti-oxidative effects in streptozotocin-induced diabetic model of inflammation and oxidative stress. METHODS: The peptides were injected intraperitoneally into the streptozotocin-induced diabetic rats and their anti-inflammatory and anti-oxidative effects were evaluated by monitoring various oxidative and inflammatory markers. RESULTS: Administration of 4F, E5 and E8 peptides decreased the oxidative and inflammatory markers in STZ-induced diabetic rats to different extent, while had no significant effect on the other diabetic parameters (viz. total body weight of animals and increased blood glucose level). E5 peptide was found to be relatively more effective than 4F and E8 peptides in decreasing inflammation and oxidative stress. CONCLUSION: E5 peptide can be developed as a potential candidate for inflammatory conditions.

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.

Differential interaction of peptides derived from C-terminal domain of human apolipoprotein E with platelet activating factor analogs.

Apolipoprotein-derived peptides are promising candidates for the treatment of various inflammatory conditions and the main mechanism proposed for the protective action of these peptides includes binding to pro-inflammatory lipid mediators with high affinity and facilitating their sequestration/metabolism/clearance in the body. Molecules that act as pro-inflammatory lipid mediators differ considerably in their molecular structures, chemical compositions and physicochemical properties. Importance of the properties of pro-inflammatory lipid mediators on the biological activity of apolipoprotein-derived peptides has not been studied in detail. In this study, we characterized the physicochemical properties of aggregates containing lyso-PAF, acetyl-PAF and butanoyl-PAF, three closely related pro-inflammatory lipid mediators, and studied their interaction with peptides derived from the C-terminal domains of human apolipoprotein E. These PAF-analogs differ only in the chemical composition of the functional groups they carry at the sn-2 positions. Our results show that physicochemical properties of aggregates containing lyso-PAF, acetyl-PAF and butanoyl-PAF differ considerably and affect their apolipoprotein-derived peptides-binding capacity.

Physicochemical properties of bacterial pro-inflammatory lipids influence their interaction with apolipoprotein-derived peptides.

Apolipoprotein-derived peptides have emerged as a promising candidate for the treatment of various inflammatory disease conditions. Multiple mechanisms have been proposed to explain the beneficiary effects of these peptides and prominent among them being high-affinity binding of peptides to pro-inflammatory lipids and facilitating their sequestration/metabolism/clearance in the body. Pro-inflammatory lipids differ considerably in their molecular structures, chemical compositions and physicochemical properties. Importance of the properties of the pro-inflammatory lipids in their ability to bind to apolipoprotein-derived peptides is not studied in details. In this study, we have characterized the interaction of synthetic peptides derived from human apolipoprotein E with lipopolysaccharide (LPS) and lipoteichoic acid (LTA), two potent bacterial pro-inflammatory lipids that differ considerably in their molecular structures and chemical compositions. Binding of the peptides to LPS and LTA was monitored by CD spectroscopy. Effect of the peptides on the biological activity of lipids was studied by monitoring the inhibition of LPS- or LTA-induced up-regulation of the inflammatory markers in the human blood cells. Physicochemical properties of lipid aggregates were determined by fluorescence spectroscopy and native PAGE. Our results show that physicochemical properties of LPS and LTA differ considerably and influence their interaction with apolipoprotein-derived peptides.