Rational design of protein-based MRI contrast agents |
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Authors: | Yang Jenny J Yang Jianhua Wei Lixia Zurkiya Omar Yang Wei Li Shunyi Zou Jin Zhou Yubin Maniccia Anna L Wilkins Mao Hui Zhao Fuqiang Malchow Russell Zhao Shumin Johnson Julian Hu Xiaoping Krogstad Eirik Liu Zhi-Ren |
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Institution: | Department of Chemistry, Center for Drug Design and Advanced Biotechnology, Georgia State University, Atlanta, Georgia 30303, USA. chejjy@langate.gsu.edu |
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Abstract: | We describe the rational design of a novel class of magnetic resonance imaging (MRI) contrast agents with engineered proteins (CAi.CD2, i = 1, 2,..., 9) chelated with gadolinium. The design of protein-based contrast agents involves creating high-coordination Gd(3+) binding sites in a stable host protein using amino acid residues and water molecules as metal coordinating ligands. Designed proteins show strong selectivity for Gd(3+) over physiological metal ions such as Ca(2+), Zn(2+), and Mg(2+). These agents exhibit a 20-fold increase in longitudinal and transverse relaxation rate values over the conventional small-molecule contrast agents, e.g., Gd-DTPA (diethylene triamine pentaacetic acid), used clinically. Furthermore, they exhibit much stronger contrast enhancement and much longer blood retention time than Gd-DTPA in mice. With good biocompatibility and potential functionalities, these protein contrast agents may be used as molecular imaging probes to target disease markers, thereby extending applications of MRI. |
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