Combinatorial evolution of high-affinity peptides that bind to the Thomsen-Friedenreich carcinoma antigen |
| |
Authors: | Landon Linda A Peletskaya Elena N Glinsky Vladislav V Karasseva Natalia Quinn Thomas P Deutscher Susan L |
| |
Affiliation: | (1) Department of Biochemistry, M121 Medical Sciences Bldg., University of Missouri, Columbia, Missouri, 65212;(2) HIV Drug Resistance Program, National Cancer Institute-FCRDC, P.O. Box B, Bldg. 539, Room 104, Frederick, Maryland, 21702-1201;(3) Department of Health Professions, E102, Vet. Med. Bldg., University of Missouri, Columbia, Missouri, 65211;(4) Research Service, Harry S Truman Memorial Veterans Administration Hospital, 800 Hospital Dr., Columbia, Missouri, 65201-5297 |
| |
Abstract: | Thomsen-Friedenreich (TF) antigen occurs on approximately 90% of human carcinomas, is likely involved in carcinoma cell homotypic aggregation, and has clinical value as a prognostic indicator and marker of metastasized cells. Previously, we isolated anti-TF antigen peptides from bacteriophage display libraries. These bound to TF antigen on carcinoma cells but were of low affinity and solubility. We hypothesized that peptide amino acid sequence changes would result in increased affinity and solubility, which would translate into improved carcinoma cell binding and increased inhibition of aggregation. The new peptides were more soluble and exhibited up to fivefold increase in affinity (Kd 60 nM). They bound cultured human breast and prostate carcinoma cells at low concentrations, whereas the earlier peptides did not. Moreover, the new peptides were potent inhibitors of homotypic aggregation. The maturated peptides will have expanded applications in basic studies of the TF antigen and particular utility as clinical carcinoma-targeting agents. |
| |
Keywords: | Bacteriophage display affinity maturation carcinoma antigen peptide glycoepitope fluorescence quenching confocal microscopy |
本文献已被 PubMed SpringerLink 等数据库收录! |
|