Solid phase peptide synthesis and TLR-5 activity analysis of pertide fragments from the Salmonella muenchen flagellin protein

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.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Master

Grantor

The University of Texas Medical Branch

Year dc:date.issued

2005

Author dc:creator

• Joseph Richard Karam

Advisor dc:contributor.advisor

• Dr. Scott R. Gilbertson, Ph.D.

Committee members dc:contributor.committeemember

• Dr. Richard B. Pyles, Ph.D
• Dr. Cornelis Elfernik, Ph.D.

• toll-like receptor
• innate immunity
• drug synthesis and design

Statement 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.

Language dc:language.iso

eng

Dc Identifier Other

etd-08222005-204822

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/215