The amyloidogenic amino acid sequence Ac-VHSSNNFGAILSS-NH 2, corresponding to the 17-29 peptide region of human amylin (hIAPP17-29), was modified by grafting a hydrophilic PEG chain in order to obtain a novel class of peptides to be used as models to study the aggregation process of the full-length IAPP. The amphiphilic feature of the pegylated peptide fragment at the N-terminus (PEG-N-hIAPP17-29) drives the aggregation process toward stable micellar clusters without fibrillogenesis, despite the presence of β-sheet interaction between peptides at pH values higher than 4.0. The hIAPP17-29-C-PEG, in which the PEG moiety is linked to the C-terminus, does not possess analogous amphiphilic character and the ability of PEG in forming H-bonds with the solvent overcomes that of the peptide chain, thereby causing peptide flocculation. The comparison with the unmodified hIAPP17-29 and the rat's peptide sequence Ac-VRSSNNLGPGLPP NH 2(rIAPP17-29) revealed the crucial role of hydrogen bonding between peptide and solvent in determining the aggregate structure and preventing fibril formation, as well as the non-negligible effect of a small amount of organic solvent in the aqueous solution which affects the aggregation process and rate.

Aggregation Properties of the Peptide Fragments Derived from the 17-29 Region of the Human and Rat IAPP: A Comparative Study with Two PEG-Conjugated Variants of the Human Sequence

MONSU' SCOLARO, Luigi;
2010-01-01

Abstract

The amyloidogenic amino acid sequence Ac-VHSSNNFGAILSS-NH 2, corresponding to the 17-29 peptide region of human amylin (hIAPP17-29), was modified by grafting a hydrophilic PEG chain in order to obtain a novel class of peptides to be used as models to study the aggregation process of the full-length IAPP. The amphiphilic feature of the pegylated peptide fragment at the N-terminus (PEG-N-hIAPP17-29) drives the aggregation process toward stable micellar clusters without fibrillogenesis, despite the presence of β-sheet interaction between peptides at pH values higher than 4.0. The hIAPP17-29-C-PEG, in which the PEG moiety is linked to the C-terminus, does not possess analogous amphiphilic character and the ability of PEG in forming H-bonds with the solvent overcomes that of the peptide chain, thereby causing peptide flocculation. The comparison with the unmodified hIAPP17-29 and the rat's peptide sequence Ac-VRSSNNLGPGLPP NH 2(rIAPP17-29) revealed the crucial role of hydrogen bonding between peptide and solvent in determining the aggregate structure and preventing fibril formation, as well as the non-negligible effect of a small amount of organic solvent in the aqueous solution which affects the aggregation process and rate.
2010
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/1897093
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