Clardy Susan M, Keliher Edmund J, Mohan James F, Sebas Matt, Benoist Christophe, Mathis Diane, Weissleder Ralph
Center for Systems Biology, Massachusetts General Hospital , 185 Cambridge Street, CPZN 5206, Boston, Massachusetts 02114, United States.
Bioconjug Chem. 2014 Jan 15;25(1):171-7. doi: 10.1021/bc4005014. Epub 2013 Dec 20.
The ability to reliably identify pancreatic β-cells would have far reaching implications for a greater understanding of β-cell biology, measurement of β-cell mass in diabetes, islet transplantation, and drug development. The glucagon-like peptide-1 receptor (GLP1R) is highly expressed on the surface of insulin producing pancreatic β-cells. Using systematic modifications of the GLP1R ligand, exendin-4, we screened over 25 compounds and identified a palette of fluorescent exendin-4 with high GLP1R binding affinity. We show considerable differences in affinity, as well as utility of the top candidates for flow cytometry and microscopy of β-cells. Some of the developed compounds should be particularly useful for basic and translational β-cell research.
能够可靠地识别胰腺β细胞对于更深入理解β细胞生物学、糖尿病中β细胞质量的测量、胰岛移植和药物开发具有深远意义。胰高血糖素样肽-1受体（GLP1R）在产生胰岛素的胰腺β细胞表面高度表达。通过对GLP1R配体艾塞那肽-4进行系统性修饰，我们筛选了超过25种化合物，并鉴定出一系列具有高GLP1R结合亲和力的荧光艾塞那肽-4。我们展示了亲和力方面的显著差异，以及顶级候选物在β细胞流式细胞术和显微镜检查中的效用。一些已开发的化合物对于基础和转化性β细胞研究应该特别有用。
