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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Vydáno v:	Nature chemical biology Ročník 3; číslo 2; s. 108 - 112
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.02.2007 Nature Publishing Group
Témata:	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
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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 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.
AbstractList	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. 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.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. 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.
Author	Meade, Gerardene Dunne, Eimear Moran, Niamh Kenny, Dermot Shields, Denis C Edwards, Richard J Foy, Martina Park, Stephen D E Devocelle, Marc Kiernan, Aoife Signac, William
Author_xml	– sequence: 1 givenname: Richard J surname: Edwards fullname: Edwards, Richard J organization: Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, UCD Conway Institute for Biomolecular and Biomedical Research, University College Dublin – sequence: 2 givenname: Niamh surname: Moran fullname: Moran, Niamh organization: Department of Clinical Pharmacology, Royal College of Surgeons in Ireland – sequence: 3 givenname: Marc surname: Devocelle fullname: Devocelle, Marc organization: Department of Pharmaceutical and Medicinal Chemistry, Centre for Synthesis and Chemical Biology, Royal College of Surgeons in Ireland – sequence: 4 givenname: Aoife surname: Kiernan fullname: Kiernan, Aoife organization: Department of Clinical Pharmacology, Royal College of Surgeons in Ireland – sequence: 5 givenname: Gerardene surname: Meade fullname: Meade, Gerardene organization: Department of Clinical Pharmacology, Royal College of Surgeons in Ireland – sequence: 6 givenname: William surname: Signac fullname: Signac, William organization: Department of Clinical Pharmacology, Royal College of Surgeons in Ireland – sequence: 7 givenname: Martina surname: Foy fullname: Foy, Martina organization: Department of Clinical Pharmacology, Royal College of Surgeons in Ireland – sequence: 8 givenname: Stephen D E surname: Park fullname: Park, Stephen D E organization: Department of Clinical Pharmacology, Royal College of Surgeons in Ireland – sequence: 9 givenname: Eimear surname: Dunne fullname: Dunne, Eimear organization: Department of Clinical Pharmacology, Royal College of Surgeons in Ireland – sequence: 10 givenname: Dermot surname: Kenny fullname: Kenny, Dermot email: dkenny@rcsi.ie organization: Department of Clinical Pharmacology, Royal College of Surgeons in Ireland – sequence: 11 givenname: Denis C surname: Shields fullname: Shields, Denis C email: denis.shields@ucd.ie organization: Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, UCD Conway Institute for Biomolecular and Biomedical Research, University College Dublin
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SubjectTerms	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
Title	Bioinformatic discovery of novel bioactive peptides
URI	https://link.springer.com/article/10.1038/nchembio854 https://www.ncbi.nlm.nih.gov/pubmed/17220901 https://www.proquest.com/docview/222745457 https://www.proquest.com/docview/19554059 https://www.proquest.com/docview/68929735 https://www.proquest.com/docview/954579035
Volume	3
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