کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2531378 1558916 2015 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Biotinylated heptapeptides substituted with a d-amino acid as platelet-activating factor inhibitors
ترجمه فارسی عنوان
هپتاپپتید های بیوتینیل شده به عنوان مهار کننده های فاکتور فعال کننده پلاکت با یک اسید آمینو اسید جایگزین می شوند
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
چکیده انگلیسی

Platelet-activating factor (PAF), a potent lipid mediator, is implicated in many inflammatory diseases, and therefore may serve as a direct target for anti-inflammatory drugs. We previously reported that synthetic biotinylated peptides having a Tyr-Lys-Asp-Gly sequence markedly inhibit PAF-induced inflammation by direct binding, and that two synthetic fluorescence-labelled heptapeptides (Lys-Trp-Tyr-Lys-Asp-Gly-Asp and d-Lys-Trp-Tyr-Lys-Asp-Gly-Asp) with high stability in plasma specifically bind to PAF-like lipids (oxidized- and lyso-phosphatidylchoine). In this study, synthetic heptapeptides (Lys-Trp-Tyr-Lys-Asp-Gly-Asp) coupled to a biotin molecule through the N-terminal amino group and ε-amino group of N-terminus Lys, (Btn)KP6 and K(Btn)P6, respectively, and their biotinylated peptides substituted with d-Lys at the N-terminus, (Btn)dKP6 and dK(Btn)P6, respectively, were investigated for their effects on PAF-induced inflammation. In the experiments using a rat model of hind paw oedema, (Btn)KP6, K(Btn)P6, (Btn)dKP6, and dK(Btn)P6 significantly inhibited PAF-induced paw oedema, with the highest inhibitory effect exhibited by dK(Btn)P6. The inhibitory effect of d-Tyr-d-Lys-d-Asp-Gly tetrapeptide on PAF-induced paw oedema was much lower than that of Tyr-Lys-Asp-Gly tetrapeptide. In the experiments using tryptophan fluorescence spectroscopy, (Btn)KP6, K(Btn)P6, (Btn)dKP6, and dK(Btn)P6 bound to PAF dose-dependently, with dK(Btn)P6 showing the strongest binding affinity, indicating that its affinity appears to be closely correlated with its inhibitory effect on PAF-induced inflammation. These results suggest that direct binding of (Btn)KP6, K(Btn)P6, (Btn)dKP6, and dK(Btn)P6 to PAF can lead to marked inhibition of PAF-induced inflammation, and these agents, particularly dK(Btn)P6, may be useful as anti-inflammatory drugs targeting PAF with high stability in plasma.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 764, 5 October 2015, Pages 202–207
نویسندگان
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