Letter abstract
Nature Chemical Biology 3, 108 - 112 (2007)
Published online: 14 January 2007 | doi:10.1038/nchembio854
Bioinformatic discovery of novel bioactive peptides
Richard J Edwards1,2,4, Niamh Moran1,4, Marc Devocelle3, Aoife Kiernan1, Gerardene Meade1, William Signac1, Martina Foy1, Stephen D E Park1, Eimear Dunne1, Dermot Kenny1 & Denis C Shields1,2
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 activity1, 2, 3, 4 and have been used in drug development5. Peptide studies typically either derive peptides from a single identified protein or (at the other extreme) screen random combinatorial peptides4, 6, 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.
- Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
- UCD Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland.
- Centre for Synthesis and Chemical Biology, Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
- These authors contributed equally to this work.
Correspondence to: Dermot Kenny1 e-mail: dkenny@rcsi.ie
Correspondence to: Denis C Shields1,2 e-mail: denis.shields@ucd.ie
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
A shortcut to peptides to modulate plateletsNature Chemical Biology News and Views (01 Feb 2007)
