TY - JOUR
T1 - Reporter protein-targeted probes for magnetic resonance imaging
AU - Strauch, Renee C.
AU - Mastarone, Daniel J.
AU - Sukerkar, Preeti A.
AU - Song, Ying
AU - Ipsaro, Jonathan J.
AU - Meade, Thomas J.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/10/19
Y1 - 2011/10/19
N2 - Contrast agents for magnetic resonance imaging are frequently employed as experimental and clinical probes. Drawbacks include low signal sensitivity, fast clearance, and nonspecificity that limit efficacy in experimental imaging. In order to create a bioresponsive MR contrast agent, a series of four Gd(III) complexes targeted to the HaloTag reporter were designed and synthesized. HaloTag is unique among reporter proteins for its specificity, versatility, and the covalent interaction between substrate and protein. In similar systems, these properties produce prolonged in vivo lifetimes and extended imaging opportunities for contrast agents, longer rotational correlation times, and increases in relaxivity (r 1) upon binding to the HaloTag protein. In this work we report a new MR contrast probe, 2CHTGd, which forms a covalent bond with its target protein and results in a dramatic increase in sensitivity. A 6-fold increase in r 1, from 3.8 to 22 mM -1s -1, is observed upon 2CHTGd binding to the target protein. This probe was designed for use with the HaloTag protein system which allows for a variety of substrates (specific for MRI, florescence, or protein purification applications) to be used with the same reporter.
AB - Contrast agents for magnetic resonance imaging are frequently employed as experimental and clinical probes. Drawbacks include low signal sensitivity, fast clearance, and nonspecificity that limit efficacy in experimental imaging. In order to create a bioresponsive MR contrast agent, a series of four Gd(III) complexes targeted to the HaloTag reporter were designed and synthesized. HaloTag is unique among reporter proteins for its specificity, versatility, and the covalent interaction between substrate and protein. In similar systems, these properties produce prolonged in vivo lifetimes and extended imaging opportunities for contrast agents, longer rotational correlation times, and increases in relaxivity (r 1) upon binding to the HaloTag protein. In this work we report a new MR contrast probe, 2CHTGd, which forms a covalent bond with its target protein and results in a dramatic increase in sensitivity. A 6-fold increase in r 1, from 3.8 to 22 mM -1s -1, is observed upon 2CHTGd binding to the target protein. This probe was designed for use with the HaloTag protein system which allows for a variety of substrates (specific for MRI, florescence, or protein purification applications) to be used with the same reporter.
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U2 - 10.1021/ja206134b
DO - 10.1021/ja206134b
M3 - Article
C2 - 21942425
AN - SCOPUS:80054769763
VL - 133
SP - 16346
EP - 16349
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 41
ER -