کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2007258 1066368 2009 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Identification of a stable chemerin analog with potent activity toward ChemR23
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Identification of a stable chemerin analog with potent activity toward ChemR23
چکیده انگلیسی

Chemerin is a novel peptide that was identified as a natural ligand for ChemR23. As it has been reported to be involved in the regulation of immune responses and adipogenesis, chemerin may have a variety of physiological functions. Chemerin is synthesized as a precursor (prochemerin) and is proteolytically activated and inactivated in sequential steps, which control its physiological roles in a coordinated manner. Chemerin-9 (chemerin148–156) was previously identified as the smallest peptide with low nanomolar potency. However, like mature chemerin, chemerin-9 is rapidly degraded and inactivated in plasma, which has limited the use of chemerin-9 in in vivo experiments. In order to identify stable chemerin analogs that facilitate in vivo studies, we synthesized a series of chemerin-9 analogs and examined intrinsic activity and metabolic stability. We identified an agonistic and metabolically stable chemerin-9 analog (d-Tyr147-[d-Ser151, d-Ala154, Tic155]chemerin148–156) that shows enhanced plasma exposure with prolonged half-life in mice upon intraperitoneal administration. Improvement of metabolic stability resulted in a reduction in the plasma free fatty acid levels in fasted mice, which cannot be accomplished by unstable-mouse chemerin-9. This reduction in plasma free fatty acids reflects the anti-lipolysis activity of chemerin-9 and analogs in mouse primary adipocytes. The discovery of a metabolically stable chemerin analog will facilitate investigation of the pharmacological roles of chemerin in vivo. Moreover, this stable chemerin analog might provide new therapeutic approaches to inflammatory diseases such as asthma and metabolic disorders such as obesity and diabetes where ChemR23 activation may be of benefit.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Peptides - Volume 30, Issue 8, August 2009, Pages 1529–1538
نویسندگان
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