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Amphiphilic oligoamide a-helix peptidomimetics inhibit islet amyloid polypeptide aggregation

Amphiphilic oligoamide a-helix peptidomimetics inhibit islet amyloid polypeptide aggregation
Amphiphilic oligoamide a-helix peptidomimetics inhibit islet amyloid polypeptide aggregation
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 ?-sheet rich aggregates. We have previously reported classes of ?-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.
0040-4039
3670-3673
Kulikov, Oleg V.
bf20410c-70eb-4abb-926e-fce32c7db6aa
Kumar, Sunil
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Magzoub, Mazin
0fc5b55d-4d27-4f56-a9e8-34f96306a204
Knipe, Peter C.
a75b6ed7-4d9b-45fc-aacc-49e9e0d0b266
Saraogi, Ishu
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Thompson, Sam
99b7e34e-fe24-401c-b7b0-64e56cbbbcb1
Miranker, Andrew D.
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Hamilton, Andrew D.
048a6c75-91bf-4555-ab12-ce885eee65dd
Kulikov, Oleg V.
bf20410c-70eb-4abb-926e-fce32c7db6aa
Kumar, Sunil
7caed983-9316-46f5-9b3f-043f377cf6f3
Magzoub, Mazin
0fc5b55d-4d27-4f56-a9e8-34f96306a204
Knipe, Peter C.
a75b6ed7-4d9b-45fc-aacc-49e9e0d0b266
Saraogi, Ishu
42a07959-549a-443c-b126-02e468963352
Thompson, Sam
99b7e34e-fe24-401c-b7b0-64e56cbbbcb1
Miranker, Andrew D.
0cbb78ef-15c1-4e76-8ffd-ed2d5b834480
Hamilton, Andrew D.
048a6c75-91bf-4555-ab12-ce885eee65dd

Kulikov, Oleg V., Kumar, Sunil, Magzoub, Mazin, Knipe, Peter C., Saraogi, Ishu, Thompson, Sam, Miranker, Andrew D. and Hamilton, Andrew D. (2015) Amphiphilic oligoamide a-helix peptidomimetics inhibit islet amyloid polypeptide aggregation. [in special issue: Memorial Symposium-in-Print for Harry Wasserman] Tetrahedron Letters, 56 (23), 3670-3673. (doi:10.1016/j.tetlet.2015.02.132).

Record type: Article

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 ?-sheet rich aggregates. We have previously reported classes of ?-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.

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Accepted/In Press date: 27 February 2015
e-pub ahead of print date: 6 March 2015
Published date: 3 June 2015
Organisations: Chemistry

Identifiers

Local EPrints ID: 403573
URI: http://eprints.soton.ac.uk/id/eprint/403573
ISSN: 0040-4039
PURE UUID: 606468b9-86aa-416c-8bb1-12033932c57f
ORCID for Sam Thompson: ORCID iD orcid.org/0000-0001-6267-5693

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Date deposited: 07 Dec 2016 09:48
Last modified: 12 Nov 2019 01:33

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Contributors

Author: Oleg V. Kulikov
Author: Sunil Kumar
Author: Mazin Magzoub
Author: Peter C. Knipe
Author: Ishu Saraogi
Author: Sam Thompson ORCID iD
Author: Andrew D. Miranker
Author: Andrew D. Hamilton

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