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Front Biosci. 2008 Jan 1;13:1716-32.

Site-specifically modified fusion proteins for molecular imaging.

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The Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, California 94305, USA.


To visualize and quantify specific molecular pathways in vivo, it is essential to develop molecular imaging probes with high target affinity and specificity. The introduction of radioisotope, fluorophores and other detectable labels onto a protein ligand in a site-specific manner without compromising its function and binding affinity has been a valuable tool for such molecular imaging. Site-specific labeling of proteins poses an enormous challenge, because the correct functional groups of one protein amidst all of the other expressed proteins containing the same range of amino acids must be accurately targeted. Chemists have developed many diverse strategies for accomplishing sit-specific modification; unnatural amino acids have been incorporated into targeted protein for site-specific modification. Enzymatic post-translational modification of proteins is an alternative approach and beneficial complement for site-specific labeling. A small peptide tag is a substrate for the enzyme that can be appended to N-, C-terminus or internal of target protein for site-specific labeling. In this review, we will discuss several valuable tags for addressing this problem, and comment on the potential usage of tagged fusion protein for molecular imaging.

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