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Bioinformatic discovery of novel bioactive peptides

Bioinformatic discovery of novel bioactive peptides
Bioinformatic discovery of novel bioactive peptides
Short synthetic oligopeptides based on regions of human proteins that encompass functional motifs are versatile reagents for understanding protein signaling and interactions. They can either mimic or inhibit the parent protein's activity and have been used in drug development. Peptide studies typically either derive peptides from a single identified protein or (at the other extreme) screen random combinatorial peptides often without knowledge of the signaling pathways targeted. Our objective was to determine whether rational bioinformatic design of oligopeptides specifically targeted to potentially signaling-rich juxtamembrane regions could identify modulators of human platelet function. High-throughput in vitro platelet function assays of palmitylated cell-permeable oligopeptides corresponding to these regions identified many agonists and antagonists of platelet function. Many bioactive peptides were from adhesion molecules, including a specific CD226-derived inhibitor of inside-out platelet signaling. Systematic screens of this nature are highly efficient tools for discovering short signaling motifs in molecular signaling pathways.
1552-4450
108-112
Edwards, Richard J
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Moran, Niamh
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Devocelle, Marc
e80de10a-6d11-4510-8cc5-5f32ac496ed0
Kiernan, Aoife
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Meade, Gerardene
6acd2745-161b-4935-ae44-9c8d9e41f9e0
Signac, William
7b7fe9b1-2e50-4e0c-9656-fd687e0a4f6d
Foy, Martina
f77f221f-1707-4fdb-a52d-4e3960402682
Park, Stephen D.E.
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Dunne, Eimear
a8d2ec0f-20e1-4ec9-9ad4-51f4c3f6ddc6
Kenny, Dermot
a54077f4-fd74-4d8c-b985-19b147275841
Shields, Denis C.
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Edwards, Richard J
9d25e74f-dc0d-455a-832c-5f363d864c43
Moran, Niamh
0685ab69-112c-4ac0-8252-4a111addce80
Devocelle, Marc
e80de10a-6d11-4510-8cc5-5f32ac496ed0
Kiernan, Aoife
2b011978-09a9-4523-8661-e29def30ec78
Meade, Gerardene
6acd2745-161b-4935-ae44-9c8d9e41f9e0
Signac, William
7b7fe9b1-2e50-4e0c-9656-fd687e0a4f6d
Foy, Martina
f77f221f-1707-4fdb-a52d-4e3960402682
Park, Stephen D.E.
8988a480-d714-4453-8322-710dd6108d59
Dunne, Eimear
a8d2ec0f-20e1-4ec9-9ad4-51f4c3f6ddc6
Kenny, Dermot
a54077f4-fd74-4d8c-b985-19b147275841
Shields, Denis C.
57ffee4f-0277-4b3d-9c7a-8c328637d8e6

Edwards, Richard J, Moran, Niamh, Devocelle, Marc, Kiernan, Aoife, Meade, Gerardene, Signac, William, Foy, Martina, Park, Stephen D.E., Dunne, Eimear, Kenny, Dermot and Shields, Denis C. (2007) Bioinformatic discovery of novel bioactive peptides. Nature Chemical Biology, 3 (2), 108-112. (doi:10.1038/nchembio854).

Record type: Article

Abstract

Short synthetic oligopeptides based on regions of human proteins that encompass functional motifs are versatile reagents for understanding protein signaling and interactions. They can either mimic or inhibit the parent protein's activity and have been used in drug development. Peptide studies typically either derive peptides from a single identified protein or (at the other extreme) screen random combinatorial peptides often without knowledge of the signaling pathways targeted. Our objective was to determine whether rational bioinformatic design of oligopeptides specifically targeted to potentially signaling-rich juxtamembrane regions could identify modulators of human platelet function. High-throughput in vitro platelet function assays of palmitylated cell-permeable oligopeptides corresponding to these regions identified many agonists and antagonists of platelet function. Many bioactive peptides were from adhesion molecules, including a specific CD226-derived inhibitor of inside-out platelet signaling. Systematic screens of this nature are highly efficient tools for discovering short signaling motifs in molecular signaling pathways.

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Published date: 14 February 2007

Identifiers

Local EPrints ID: 46487
URI: http://eprints.soton.ac.uk/id/eprint/46487
ISSN: 1552-4450
PURE UUID: add329c3-6eb8-4194-87e6-37b5fa320300

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Date deposited: 03 Jul 2007
Last modified: 15 Mar 2024 09:24

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Contributors

Author: Richard J Edwards
Author: Niamh Moran
Author: Marc Devocelle
Author: Aoife Kiernan
Author: Gerardene Meade
Author: William Signac
Author: Martina Foy
Author: Stephen D.E. Park
Author: Eimear Dunne
Author: Dermot Kenny
Author: Denis C. Shields

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