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 D. Hamilton

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

LanguageEnglish
Pages3670-3673
Number of pages4
JournalTetrahedron Letters
Volume56
Issue number23
Early online date06 Mar 2015
DOIs
Publication statusPublished - 03 Jun 2015
Externally publishedYes

Fingerprint

Islet Amyloid Polypeptide
Peptidomimetics
Agglomeration
Lipid bilayers
Lipid Bilayers
Medical problems
Scaffolds
Rigidity
Type 2 Diabetes Mellitus
Alzheimer Disease
Proteins
Lipids
alpha-Helical Protein Conformation
benzamide
beta-Strand Protein Conformation

Keywords

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

Cite this

Kulikov, O. V., Kumar, S., Magzoub, M., Knipe, P. C., Saraogi, I., Thompson, S., ... Hamilton, A. D. (2015). Amphiphilic oligoamide α-helix peptidomimetics inhibit islet amyloid polypeptide aggregation. Tetrahedron Letters, 56(23), 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 D. / 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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Kulikov, OV, Kumar, S, Magzoub, M, Knipe, PC, Saraogi, I, Thompson, S, Miranker, AD & Hamilton, AD 2015, 'Amphiphilic oligoamide α-helix peptidomimetics inhibit islet amyloid polypeptide aggregation', Tetrahedron Letters, vol. 56, no. 23, pp. 3670-3673. https://doi.org/10.1016/j.tetlet.2015.02.132

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 D.

In: Tetrahedron Letters, Vol. 56, No. 23, 03.06.2015, p. 3670-3673.

Research output: Contribution to journalArticle

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