Amphiphilic oligoamide α-helix peptidomimetics inhibit islet amyloid polypeptide aggregation

Oleg V. Kulikov, Sunil Kumar, Mazin Magzoub, Peter C. Knipe, Ishu Saraogi, Sam Thompson, Andrew D. Miranker, Andrew Hamilton

Research output: Contribution to journalArticle

Abstract

Abstract The abnormal deposition of proteins as insoluble plaques is associated with many diseases, including Alzheimer's, Parkinson's and type II diabetes. There is an unmet need for synthetic agents that are able to mediate particular steps in the pathway between soluble proteins in their native unfolded state and their insoluble β-sheet rich aggregates. We have previously reported classes of α-helix mimetic that agonize or antagonize islet amyloid polypeptide aggregation, depending on the presence of a lipid bilayer. Here we investigate a novel mixed benzamide and pyridylamide scaffold that gives improved activity and explores the role of side-chain polarity, backbone rigidity and curvature in inhibiting lipid-catalyzed fibrillization.

Original languageEnglish (US)
Article number46004
Pages (from-to)3670-3673
Number of pages4
JournalTetrahedron Letters
Volume56
Issue number23
DOIs
StatePublished - Jan 21 2015

Fingerprint

Islet Amyloid Polypeptide
Peptidomimetics
Agglomeration
Lipid bilayers
Lipid Bilayers
Medical problems
Scaffolds
Rigidity
Type 2 Diabetes Mellitus
Alzheimer Disease
Proteins
Lipids
benzamide

Keywords

  • Amyloid β-peptides
  • Diabetes
  • Helical structures
  • Proteomimetics
  • α-Helix mimetics

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Amphiphilic oligoamide α-helix peptidomimetics inhibit islet amyloid polypeptide aggregation. / Kulikov, Oleg V.; Kumar, Sunil; Magzoub, Mazin; Knipe, Peter C.; Saraogi, Ishu; Thompson, Sam; Miranker, Andrew D.; Hamilton, Andrew.

In: Tetrahedron Letters, Vol. 56, No. 23, 46004, 21.01.2015, p. 3670-3673.

Research output: Contribution to journalArticle

Kulikov, OV, Kumar, S, Magzoub, M, Knipe, PC, Saraogi, I, Thompson, S, Miranker, AD & Hamilton, A 2015, 'Amphiphilic oligoamide α-helix peptidomimetics inhibit islet amyloid polypeptide aggregation', Tetrahedron Letters, vol. 56, no. 23, 46004, pp. 3670-3673. https://doi.org/10.1016/j.tetlet.2015.02.132
Kulikov, Oleg V. ; Kumar, Sunil ; Magzoub, Mazin ; Knipe, Peter C. ; Saraogi, Ishu ; Thompson, Sam ; Miranker, Andrew D. ; Hamilton, Andrew. / Amphiphilic oligoamide α-helix peptidomimetics inhibit islet amyloid polypeptide aggregation. In: Tetrahedron Letters. 2015 ; Vol. 56, No. 23. pp. 3670-3673.
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