A facile, click chemistry-based approach to assembling fluorescent chemosensors for protein tyrosine kinases.
A group of fluorophore-labeled peptide substrates of Src kinases have been synthesized with the aid of click chemistry. Some of the generated peptides exhibit an increase in fluorescence upon phosphorylation and are capable of detecting Src kinases with high sensitivity and specificity. Their availability permits real-time activity measurement of aberrantly activated oncogenic Src kinases in the crude lysate of chronic myelogenous leukemia cells. These new chemosensor peptides are highly useful tools that can be used for high-throughput screening to search for small molecule inhibitors of Src kinases as potential therapeutics for cancer treatment.
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, 3010 Victoria, Australia.
Mohd Aizuddin
MA
Kamaruddin
Phuc
P
Ung
Mohammed Iqbal
MI
Hossain
Boonyarin
B
Jarasrassamee
William
W
O'Malley
Philip
P
Thompson
Denis
D
Scanlon
Heung-Chin
HC
Cheng
Bim
B
Graham
D000595:Amino Acid Sequence; D015374:Biosensing Techniques; D045744:Cell Line, Tumor; D057930:Click Chemistry; D057075:Enzyme Assays / Q000379:methods*; D005456:Fluorescent Dyes / Q000737:chemistry*; D057166:High-Throughput Screening Assays; D006801:Humans; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D013379:Substrate Specificity; D019061:src-Family Kinases / Q000378:metabolism*
D005456:Fluorescent Dyes; D010455:Peptides; D019061:src-Family Kinases