A foldamer approach to targeting membrane bound helical states of islet amyloid polypeptide.
نویسندگان
چکیده
A small molecule, protein mimetic based approach is shown to specifically inhibit lipid catalysed self-assembly of islet amyloid polypeptide (IAPP). The lipid-bound oligomerization of this peptide is implicated in cellular dysfunction of insulin secreting β-cells in type II diabetes.
منابع مشابه
Conserved and cooperative assembly of membrane-bound alpha-helical states of islet amyloid polypeptide.
The conversion of soluble protein into beta-sheet-rich amyloid fibers is the hallmark of a number of serious diseases. Precursors for many of these systems (e.g., Abeta from Alzheimer's disease) reside in close association with a biological membrane. Membrane bilayers are reported to accelerate the rate of amyloid assembly. Furthermore, membrane permeabilization by amyloidogenic peptides can le...
متن کاملFolded small molecule manipulation of islet amyloid polypeptide.
Islet amyloid polypeptide (IAPP) is a hormone cosecreted with insulin by pancreatic β cells. Upon contact with lipid bilayers, it is stabilized into a heterogeneous ensemble of structural states. These processes are associated with gains of function, including catalysis of β sheet-rich amyloid formation, cell membrane penetration, loss of membrane integrity, and cytotoxicity. These contribute t...
متن کاملIslet Amyloid Polypeptide is not a Target Antigen for CD8+ T-Cells in Type 2 Diabetes
Background: Type 2 diabetes (T2D) is a chronic metabolic disorder in which beta-cells are destroyed. The islet amyloid polypeptide (IAPP) produced by beta-cells has been reported to influence beta-cell destruction. Objective: To evaluate if IAPP can act as an autoantigen and therefore, to see if CD8 + T-cells specific for this protein might be present in T2D patients. Methods: Peripheral blood ...
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Islet amyloid polypeptide (IAPP or amylin) is a 37-residue peptide hormone associated with glucose metabolism that is cosecreted with insulin by beta-cells in the pancreas. Since human IAPP is a highly amyloidogenic peptide, it has been suggested that the formation of IAPP amyloid fibers is responsible for the death of beta-cells during the early stages of type II diabetes. It has been hypothes...
متن کاملα-Helical Structures Drive Early Stages of Self-Assembly of Amyloidogenic Amyloid Polypeptide Aggregate Formation in Membranes
The human islet amyloid polypeptide (hIAPP) is the primary component in the toxic islet amyloid deposits in type-2 diabetes. hIAPP self-assembles to aggregates that permeabilize membranes and constitutes amyloid plaques. Uncovering the mechanisms of amyloid self-assembly is the key to understanding amyloid toxicity and treatment. Although structurally similar, hIAPP's rat counterpart, the rat i...
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ورودعنوان ژورنال:
- Chemical communications
دوره 49 42 شماره
صفحات -
تاریخ انتشار 2013