A novel peptide defined through phage display for therapeutic protein and vector neuronal targeting
A novel peptide with the binding characteristics of tetanus toxin was identified with phage display, for application in therapeutic protein and vector motor and sensory neuron targeting. A 12mer phage library was biopanned on trisialoganglioside (GT1b) and eluted with the tetanus toxin C fragment (r...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2005-08-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999610500032X |
| _version_ | 1818721778590023680 |
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| author | James K. Liu Qingshan Teng Mary Garrity-Moses Thais Federici Diana Tanase Michael J. Imperiale Nicholas M. Boulis |
| author_facet | James K. Liu Qingshan Teng Mary Garrity-Moses Thais Federici Diana Tanase Michael J. Imperiale Nicholas M. Boulis |
| author_sort | James K. Liu |
| collection | DOAJ |
| description | A novel peptide with the binding characteristics of tetanus toxin was identified with phage display, for application in therapeutic protein and vector motor and sensory neuron targeting. A 12mer phage library was biopanned on trisialoganglioside (GT1b) and eluted with the tetanus toxin C fragment (rTTC). Phage ELISAs revealed increases in GT1b binding for the Tet1 and Tet2 phage clones when compared to peptideless phage (PLP). rTTC displaced both Tet1 and Tet2 phage clones from GT1b, and both clones reduced rTTC-GT1b binding. Comparison of Tet1, Tet2, PLP, and the random phage library binding to PC12 and HEK293 cells revealed enhanced cellular binding by Tet1 and Tet2 phage. Tet1 phage binding was selective for neurons. Immunofluorescence also confirmed selective PC12 binding of Tet1 and Tet2 phage. Fluorescein-conjugated synthetic Tet1, but not Tet2, peptide showed strong binding to cultured PC12, primary motor neurons, and dorsal root ganglion (DRG) cells. Synthetic Tet1 bound DRG and motor neurons but not muscle in tissue sections. The enhanced neuronal binding affinity and specificity of Tet1, a novel 12 amino acid peptide, suggests potential utility for targeting neurotherapeutic proteins and viral vectors in the treatment of motor neuron disease, neuropathy, and pain. |
| first_indexed | 2024-12-17T20:44:08Z |
| format | Article |
| id | doaj.art-145aa52bf79342f19e5fed3f18b7b2ac |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T20:44:08Z |
| publishDate | 2005-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-145aa52bf79342f19e5fed3f18b7b2ac2022-12-21T21:33:12ZengElsevierNeurobiology of Disease1095-953X2005-08-01193407418A novel peptide defined through phage display for therapeutic protein and vector neuronal targetingJames K. Liu0Qingshan Teng1Mary Garrity-Moses2Thais Federici3Diana Tanase4Michael J. Imperiale5Nicholas M. Boulis6Department of Neuroscience and Center for Neurological Restoration, NB2-126, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Neuroscience and Center for Neurological Restoration, NB2-126, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Neuroscience and Center for Neurological Restoration, NB2-126, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Neuroscience and Center for Neurological Restoration, NB2-126, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Neuroscience and Center for Neurological Restoration, NB2-126, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USADepartment of Neuroscience and Center for Neurological Restoration, NB2-126, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Corresponding author. Fax: +1 216 445 1466.A novel peptide with the binding characteristics of tetanus toxin was identified with phage display, for application in therapeutic protein and vector motor and sensory neuron targeting. A 12mer phage library was biopanned on trisialoganglioside (GT1b) and eluted with the tetanus toxin C fragment (rTTC). Phage ELISAs revealed increases in GT1b binding for the Tet1 and Tet2 phage clones when compared to peptideless phage (PLP). rTTC displaced both Tet1 and Tet2 phage clones from GT1b, and both clones reduced rTTC-GT1b binding. Comparison of Tet1, Tet2, PLP, and the random phage library binding to PC12 and HEK293 cells revealed enhanced cellular binding by Tet1 and Tet2 phage. Tet1 phage binding was selective for neurons. Immunofluorescence also confirmed selective PC12 binding of Tet1 and Tet2 phage. Fluorescein-conjugated synthetic Tet1, but not Tet2, peptide showed strong binding to cultured PC12, primary motor neurons, and dorsal root ganglion (DRG) cells. Synthetic Tet1 bound DRG and motor neurons but not muscle in tissue sections. The enhanced neuronal binding affinity and specificity of Tet1, a novel 12 amino acid peptide, suggests potential utility for targeting neurotherapeutic proteins and viral vectors in the treatment of motor neuron disease, neuropathy, and pain.http://www.sciencedirect.com/science/article/pii/S096999610500032XDorsal root ganglionGangliosideMotor neuronPhage displayTetanus toxin C fragment |
| spellingShingle | James K. Liu Qingshan Teng Mary Garrity-Moses Thais Federici Diana Tanase Michael J. Imperiale Nicholas M. Boulis A novel peptide defined through phage display for therapeutic protein and vector neuronal targeting Neurobiology of Disease Dorsal root ganglion Ganglioside Motor neuron Phage display Tetanus toxin C fragment |
| title | A novel peptide defined through phage display for therapeutic protein and vector neuronal targeting |
| title_full | A novel peptide defined through phage display for therapeutic protein and vector neuronal targeting |
| title_fullStr | A novel peptide defined through phage display for therapeutic protein and vector neuronal targeting |
| title_full_unstemmed | A novel peptide defined through phage display for therapeutic protein and vector neuronal targeting |
| title_short | A novel peptide defined through phage display for therapeutic protein and vector neuronal targeting |
| title_sort | novel peptide defined through phage display for therapeutic protein and vector neuronal targeting |
| topic | Dorsal root ganglion Ganglioside Motor neuron Phage display Tetanus toxin C fragment |
| url | http://www.sciencedirect.com/science/article/pii/S096999610500032X |
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