title: The quest for the shortest fragments of A (13-19) and B (12-17) responsible for the aggregation of human insulin.
abstract: To identify the shortest components of A13-A19, B12-B17 fragments capable for fibrillation and to validate the dependability of aggregation on the presence of hydroxyl group engaged in the 'tyrosine kissing'.
  
  
  
  Fragments A13-A19 and B12-B17 of insulin and all shortened analogues were obtained by using DMT/NMM/TosO(-) as a coupling reagent. The aggregation was studied by three independent tests.
  
  
  
  Studies on the susceptibility to aggregation of truncated analogs of insulin amyloidogenic core show three groups of peptides.
  
  
  
  Truncation of A13-A419 fragment shows that fibrous structures are formed by all peptides bearing (13)H-LeuTyr-OH(14). Propensity to aggregation was found for (16)H-TyrLeu-OH(17) B12-B17 fragment. Tyrosine residue modification by incorporation of tert-butyl group on hydroxyl function gave analogues still predisposed to aggregation.
authors.affiliation: Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Swiontek
authors.affiliation: Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Rozniakowski
authors.affiliation: Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Fraczyk
authors.affiliation: Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Lipinski
authors.affiliation: Institute of General Food Chemistry, Faculty of Biotechnology & Food Sciences, Lodz University of Technology, Stefanowskiego 4/10, 90-924 Lodz, Poland.
authors.forename: Krystian
authors.initials: K
authors.lastname: Galecki
authors.affiliation: Institute of General Food Chemistry, Faculty of Biotechnology & Food Sciences, Lodz University of Technology, Stefanowskiego 4/10, 90-924 Lodz, Poland.
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Wysocki
authors.affiliation: Department of Molecular Physics, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
authors.forename: Bertrand G
authors.initials: BG
authors.lastname: R Dupont
authors.affiliation: Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
authors.forename: Zbigniew J
authors.initials: ZJ
authors.lastname: Kaminski
authors.affiliation: Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Kolesinska
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007328:Insulin / Q000737:chemistry* / Q000378:metabolism; D007930:Leucine / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
chemical_list: D000682:Amyloid; D007328:Insulin; D010446:Peptide Fragments; D066329:Protein Aggregates; D014443:Tyrosine; D007930:Leucine
keywords: aggregation; amyloid-like structure; diabetes; hydrophobic interaction; nanofibril; triazine coupling reagent; tyrosine residue; π–π interaction