Clinical Chemistry
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Clinical Chemistry 44: 232-238, 1998;
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(Clinical Chemistry. 1998;44:232-238.)
© 1998 American Association for Clinical Chemistry, Inc.

Enzymes and Protein Markers

Combinatorial search for diagnostic agents: Lyme antibody H9724 as an example

Jian Tu, Zhiguang Yu, and Yen-Ho Chua

Department of Chemistry, The Ohio State University, Columbus, OH 43210.
a Author for correspondence. Fax 614-292-1685; e-mail chu{at}chemistry.ohio-state.edu.

Two peptide libraries, Ac-MXXXXXBBRM and Ac-VXXXXXBBRM, were constructed on TentaGel solid support to search for ligands that bind tightly with the H9724 Lyme antibody. By using an on-bead ELISA, approximately 120 ligands were selected as candidates for further study. Matrix-assisted laser desorption ionization mass spectrometry analysis of the candidate ligands indicated a high rate of occurrence of certain amino acids at the randomized positions. On the basis of the initial screening results, a small library was designed and iteratively synthesized. Subsequent library screenings led to the identification of four peptides, Ac-PQEEGX-NH2 (X = R, K, A, D), that showed specific affinity to the antibody. This combination of solid-phase screening and iterative synthesis is an effective strategy for rapid identification of ligands that bind tightly with disease-specific antibodies and should be applicable, at least in principle, to other ligand-receptor systems. This combinatorial library approach can also be a useful tool for the discovery of novel diagnostic agents.




The following articles in journals at HighWire Press have cited this article:


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M. Bagheri, M. Beyermann, and M. Dathe
Immobilization Reduces the Activity of Surface-Bound Cationic Antimicrobial Peptides with No Influence upon the Activity Spectrum
Antimicrob. Agents Chemother., March 1, 2009; 53(3): 1132 - 1141.
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G. A. Kouzmitcheva, V. A. Petrenko, and G. P. Smith
Identifying Diagnostic Peptides for Lyme Disease through Epitope Discovery
Clin. Vaccine Immunol., January 1, 2001; 8(1): 150 - 160.
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