• Nuclear Medicine and Molecular Imaging
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• v.41 no.4
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• pp.326-334
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• 2007

Purpose: The estrogen receptor (ER), which is over-expressed in ER-positive breast tumors, has been imaged by positron emission tomography (PET) using $[^{18}F]$ labeled estrogen ligands, especially $[^{18}F]FES$. However, $[^{18}F]$ has relatively short-lived half-life ($t_{1/2}$ =1.8 h) and the labeling yield of radio-fluorination is usually low compared with $^{64}Cu\;(t_{1/2}=12.7\;h)$. 1,4,7,10-tetraazacyclododecane (cyclen) is used to form stable metal complexes with copper, indium, gallium, and gadolinium. With these in mind, we prepared cyclen-based Cu complexes which mimic estradiol in aspect of two hydroxyl groups. Materials and Methods: 1.7-Protected cyclen, 1.7-bis (benzyloxycarbonyl)-cyclen was synthesized according to the reported procedure. After introducing two 4-benzyloxybenzyl groups at 4,10-positions, the benzyloxycarbonyl and benzyl groups were removed at the same time by hydrogenation on Pd/C to give 1,7-bis(4-hydroxybenzyl)-1,4,7,10-tetraazacyclododecane (1). Results: The prepared ligand 1 was fully characterized by $^1H,\;^{13}C$ NMR, and mass spectrometer. The synthesized ligand was reacted with copper chloride and copper perchlorate to give copper complexes $[Cu(1)]^{2+}2(CIO_4^-)\;and\;[Cu(1)Cl]^+Cl^-$ which were confirmed by high-resolution mass (FAB). Conclusion: We successfully synthesized a cyclen derivative of which two phenol groups are located on trans position of N-atoms. And, two Cu(ll) complexes of +2 and +1 overall charge, were prepared as a potential PET tracers for ER imaging.

• Bulletin of the Korean Chemical Society
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• v.25 no.12
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• pp.1917-1923
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• 2004

Although the proteolytic activity of the Cu(II) complex of cyclen (Cyc) is greatly enhanced upon attachment to a cross-linked polystyrene (PS), the Cu(II)Cyc-containing PS derivatives reported previously hydrolyzed only a very limited number of proteins. The PS-based artificial metalloproteases can overcome thermal, mechanical, and chemical instabilities of natural proteases, but the narrow substrate selectivity of the artificial metalloproteases limits their industrial application. In the present study, artificial metalloproteases exhibiting broad substrate selectivity were synthesized by attaching Cu(II)Cyc to a PS derivative using linkers with various structures in an attempt to facilitate the interaction of various protein substrates with the PS surface. The new artificial metalloproteases hydrolyzed all of the four protein substrates (albumin, myoglobin, ${\gamma}$-globulin, and lysozyme) examined, manifesting $k_{cat}/K_m$ values of 28-1500 $h_{-1}M_{-1}$ at 50 $^{\circ}C$. The improvement in substrate selectivity is attributed to steric and/or polar interaction between the bound protein and the PS surface as well as the hydrophobicity of the microenvironment of the catalytic centers.