Development of a seaweed derived platelet activating factor acetylhydrolase (PAF-AH) inhibitory hydrolysate, synthesis of inhibitory peptides and assessment of their toxicity using the Zebrafish larvae assay

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• 作者：Ciar谩n Fitzgerald ; Eimear Gallagher ; Paula O鈥機onnor ; Jos茅 Prieto ; Leticia Mora-Soler ; Maura Grealy ; Maria Hayes
• 关键词：Atherosclerosis ; Lp-PLA2 ; Enzyme inhibition ; Darapladib ; Platelet-activating factor acetylhydrolase ; Bioactive peptides ; Palmaria palmata
• 刊名：Peptides
• 出版年：December, 2013
• 年：2013
• 卷：50
• 期：Complete
• 页码：119-124
• 全文大小：1009 K

文摘

The vascular inflammatory role of platelet activating factor acetylhydrolase (PAF-AH) is thought to be due to the formation of lysophosphatidyl choline and oxidized non-esterified fatty acids. This enzyme is considered a promising therapeutic target for the prevention of atherosclerosis and there is a need to expand the available chemical templates of PAF-AH inhibitors. This study demonstrated how natural PAF-AH inhibitory peptides were isolated and characterized from the red macroalga Palmaria palmata. The dried powdered alga was hydrolyzed using the food grade enzyme papain, and the resultant peptide containing fraction generated using RP-HPLC. Several oligopeptides were identified as potential PAF-AH inhibitors following bio-guided fractionation, and the amino acid sequences of these oligopeptides were confirmed by Q-TOF-MS and microwave-assisted solid phase de novo synthesis. The most promising PAF-AH inhibitory peptide had the amino acid sequence NIGK and a PAF-AH IC₅₀ value of 2.32 mM. This peptide may constitute a valid drug template for PAF-AH inhibitors. Furthermore the P. palmata hydrolysate was nontoxic when assayed using the Zebrafish toxicity model at a concentration of 1 mg/ml.