Amyloidogenesis of the amylin analogue pramlintide.
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.
School of Pharmacy, Federal University of Rio de Janeiro - UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil.
Dayana Cabral
DC
da Silva
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.
Giselle N
GN
Fontes
School of Pharmacy, Federal University of Rio de Janeiro - UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil.
Luiza C S
LC
Erthal
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; National Institute of Science and Technology for Structural Biology and Bioimaging (INBEB-INCT), Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, Brazil. Electronic address: LML@UFRJ.BR.
Luís Maurício T R
LM
Lima
D000682:Amyloid / Q000138:chemical synthesis*; D052160:Benzothiazoles; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000737:chemistry; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide / Q000737:chemistry*; D007700:Kinetics; D013058:Mass Spectrometry; D008853:Microscopy; D012995:Solubility; D013844:Thiazoles; D014961:X-Ray Diffraction
D000682:Amyloid; D052160:Benzothiazoles; D007004:Hypoglycemic Agents; D058228:Islet Amyloid Polypeptide; D013844:Thiazoles; C009462:thioflavin T; C105254:pramlintide
Amylin; Amyloid; Diabetes; Islet associated polypeptide; Pramlintide