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 1 , 2 , 3 , 4 and have been used in drug development 5 ....

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Veröffentlicht in:	Nature chemical biology Jg. 3; H. 2; S. 108 - 112
Hauptverfasser:	Edwards, Richard J, Moran, Niamh, Devocelle, Marc, Kiernan, Aoife, Meade, Gerardene, Signac, William, Foy, Martina, Park, Stephen D E, Dunne, Eimear, Kenny, Dermot, Shields, Denis C
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	New York Nature Publishing Group US 01.02.2007 Nature Publishing Group
Schlagworte:	Adenosine Diphosphate - secretion Adhesion Amino Acid Sequence Antigens, Differentiation, T-Lymphocyte - genetics Antigens, Differentiation, T-Lymphocyte - metabolism Biochemical Engineering Biochemistry Bioinformatics Biology Bioorganic Chemistry Blood Platelets - drug effects Blood Platelets - metabolism Cell Adhesion Molecules - genetics Cell Biology Chemistry Chemistry and Materials Science Chemistry/Food Science Cluster Analysis Computational Biology - methods Drug Evaluation, Preclinical Humans letter Membrane Proteins - genetics Molecular Mimicry - genetics Oligopeptides - chemistry Oligopeptides - genetics Oligopeptides - pharmacology Palmitic Acid - chemistry Peptide Fragments - genetics Peptide Fragments - pharmacology Peptides Platelet Activation - drug effects Platelet Aggregation - drug effects Platelet Aggregation Inhibitors - chemistry Platelet Aggregation Inhibitors - pharmacology Platelet Glycoprotein GPIIb-IIIa Complex - metabolism Proteins Reagents Signal transduction
ISSN:	1552-4450, 1552-4469
Online-Zugang:	Volltext
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Zusammenfassung:	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 1 , 2 , 3 , 4 and have been used in drug development 5 . Peptide studies typically either derive peptides from a single identified protein or (at the other extreme) screen random combinatorial peptides 4 , 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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23
ISSN:	1552-4450 1552-4469
DOI:	10.1038/nchembio854