da Silva Dayana Cabral, Fontes Giselle N, Erthal Luiza C S, Lima Luís Maurício T R
School of Pharmacy, Federal University of Rio de Janeiro - UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil.
Laboratory for Macromolecules (LAMAC-DIMAV), Brazilian National Institute of Metrology, Quality and Technology - INMETRO, Av. N. Sa. das Graças, 50 - Xerém, Duque de Caxias 25250-020, Rio de Janeiro, Brazil.
Biophys Chem. 2016 Dec;219:1-8. doi: 10.1016/j.bpc.2016.09.007. Epub 2016 Sep 20.
Amylin is a pancreatic peptide hormone co-secreted along with insulin by the β-cells. It is found in amyloid deposits in both type 2 diabetic individuals and elder non-diabetic. The triple proline amylinomimetic compound (25,28,29-Pro-human amylin) named pramlintide was designed aiming to solve the solubility and amyloid characteristics of human amylin. We have found by using ion mobility spectrometry-based mass spectrometry that pramlintide is able to assembly into multimers. Pramlintide formed amyloid fibrils in vitro in a pH-dependent kinetic process within a few hours, as followed by thioflavin T, quantification of soluble peptide and further characterized by transmission electron microscopy, atomic force microscopy and X-ray diffraction. These data indicate that pramlintide can form amyloid fibers.
胰淀素是一种与胰岛素由β细胞共同分泌的胰腺肽激素。在2型糖尿病患者和老年非糖尿病患者的淀粉样沉积物中均可发现它。设计了一种名为普兰林肽的三脯氨酸类胰淀素模拟化合物（25,28,29-脯氨酸-人胰淀素），旨在解决人胰淀素的溶解性和淀粉样特性问题。我们通过基于离子淌度光谱的质谱法发现，普兰林肽能够组装成多聚体。普兰林肽在体外数小时内通过硫黄素T、可溶性肽定量以及随后的透射电子显微镜、原子力显微镜和X射线衍射进一步表征，在pH依赖性动力学过程中形成淀粉样纤维。这些数据表明普兰林肽可以形成淀粉样纤维。
