Solid phase peptide synthesis and TLR-5 activity analysis of pertide fragments from the Salmonella muenchen flagellin protein
| dc.contributor.advisor | Dr. Scott R. Gilbertson, Ph.D. | en_US |
| dc.contributor.committeeMember | Dr. Richard B. Pyles, Ph.D | en_US |
| dc.contributor.committeeMember | Dr. Cornelis Elfernik, Ph.D. | en_US |
| dc.creator | Joseph Richard Karam | en_US |
| dc.date.accessioned | 2011-12-20T16:05:13Z | |
| dc.date.available | 2008-06-17 | en_US |
| dc.date.available | 2011-12-20T16:05:13Z | |
| dc.date.created | 2005-08-22 | en_US |
| dc.date.issued | 2005-08-18 | en_US |
| dc.description.abstract | Drug design strategies begin by determining the simplest ligand necessary to activate a receptor of interest. The Toll-Like Receptor-5 (TLR-5) is an attractive target for pharmaceutical modulation because it initiates an innate immune response. A TLR-5 agonist or antagonist could help remedy a variety of disorders. Flagellin, the primary component of bacterial flagella, is the only known TLR-5 ligand. Three short regions within this protein are suggested to activate TLR-5: Peptide-N1, LQRVRELAVQ; Peptide-N2, LAVQSANGTNSQSD; and Peptide-C1, QNRFNSAITNLGNT. Here, we report the synthesis of these peptides and their activity against TLR-5 expressing HEK-293 cells. Our goal was to resolve the minimal region of flagellin necessary to bind and/or activate TLR-5. Results showed significant agonist activity (P<0.01) with peptide N2-b (LAVQSANGTN), and peptide N2-f (LAVQSANGTNSQ). Peptide N2-c (ANGTN) and N2-d (LAVQS) showed significant (P<0.05) antagonistic properties for TLR-5. These peptides could make interesting lead compounds to modify for optimal TLR-5 activity. | en_US |
| dc.format.medium | electronic | en_US |
| dc.identifier.other | etd-08222005-204822 | en_US |
| dc.identifier.uri | http://hdl.handle.net/2152.3/215 | |
| dc.language.iso | eng | en_US |
| dc.rights | Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works. | en_US |
| dc.subject | toll-like receptor | en_US |
| dc.subject | innate immunity | en_US |
| dc.subject | drug synthesis and design | en_US |
| dc.title | Solid phase peptide synthesis and TLR-5 activity analysis of pertide fragments from the Salmonella muenchen flagellin protein | en_US |
| dc.type.genre | thesis | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Pharmacology and Toxicology | en_US |
| thesis.degree.grantor | The University of Texas Medical Branch | en_US |
| thesis.degree.level | Master | en_US |
| thesis.degree.name | Master of Science | en_US |