BACKBONE-MODIFIED AMYLIN DERIVATIVES: IMPLICATIONS FOR AMYLOID INHIBITOR DESIGN AND AS TEMPLATE FOR SELF-ASSEMBLED BIONANOMATERIALS

摘要

Uncontrolled aggregation of proteins/polypeptides leading to the formation of amyloid fibrils is a major cause of a number of diseases. Examples of these so-called amyloid-diseases are Alzheimer's disease, Parkinson's disease, transmissible spongiform encephalopathies and diabetes type II. The latter is characterized by deposits of islet amyloid polypeptide (IAPP, or amylin) which are present in the pancreatic islets. Amyloid fibrils are characterized by the (anti)parallel organization of β-pleated sheets which lead to a reduced solubility of the protein/polypeptide and to the formation of deposits of amyloid plaques. A well accepted approach to interfere with β-sheet formation is the design of soluble β-sheet peptides to disrupt the hydrogen bonding network which ultimately leads to the disassembly of the amyloid fibrils.