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Effective combinatorial strategy to increase affinity of carbohydrate binding by peptides
Linda A Landon1, Jun Zou, Susan L Deutscher
1Department of Biochemistry, M743 Medical Sciences Bldg., University of Missouri, Columbia, MO, USA.
Molecular Diversity
|February 18, 2004
Summary
Researchers enhanced antigen-binding peptides targeting the Thomsen-Friedenreich antigen, a cancer marker. These improved peptides show higher affinity and solubility, advancing diagnostic and therapeutic applications for carcinoma.
Area of Science:
- Biochemistry
- Molecular Biology
- Carcinogenesis
Background:
- The Thomsen-Friedenreich antigen is a disaccharide linked to carcinoma cell aggregation and metastasis.
- Antigen-binding macromolecules show potential as diagnostic and therapeutic agents for cancer.
- First-generation peptides targeting this antigen were previously selected using bacteriophage display.
Purpose of the Study:
- To investigate if targeted sequence space exploration around a consensus sequence improves peptide affinity and solubility.
- To develop enhanced peptides for targeting carcinoma cells and inhibiting aggregation.
Main Methods:
- Combinatorial affinity maturation of antigen-binding peptides.
- In vitro analysis of peptide sequence evolution, solubility, and binding affinity.
- Structure/function studies of peptide modifications.
Main Results:
- Preferential evolution of the amino-terminal sequence of peptides was observed.
- Maturated peptides exhibited increased solubility compared to first-generation peptides.
- Two maturated peptides (P-30-1, F03) demonstrated higher affinity for the Thomsen-Friedenreich antigen and stronger binding to carcinoma cells.
Conclusions:
- Affinity maturation can significantly improve carbohydrate-binding affinity in small, soluble peptides.
- This study represents the first report of maturation of carbohydrate-binding affinity in peptides.
- Enhanced peptides hold promise for in vivo diagnostic and therapeutic applications in carcinoma.