Biophysical Characterization of Human Protamine-1 as a Responsive CEST MR Contrast Agent.

Biophysical Characterization of Human Protamine-1 as a Responsive CEST MR Contrast Agent.
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DOI:
10.1021/mz500681y
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发表时间:
2015-01-20
期刊:
影响因子:
7.015
通讯作者:
McMahon MT
McMahon MT
中科院分区:
化学1区
文献类型:
--
作者:
Oskolkov N;Bar-Shir A;Chan KW;Song X;van Zijl PC;Bulte JW;Gilad AA;McMahon MT

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The protamines are a low-molecular-weight, arginine-rich family of nuclear proteins that protect chromosomal DNA in germ cells by packing it densely using electrostatic interactions. Human protamine-1 (hPRM1) has been developed as a magnetic resonance imaging (MRI) chemical exchange saturation transfer (CEST) reporter gene, based on a sequence that is approximately 50% arginine, which has a side chain with rapidly exchanging protons. In this study, we have synthesized hPRM1 and determined how its CEST MRI contrast varies as a function of pH, phosphorylation state, and upon noncovalent interaction with nucleic acids and heparin (as antagonist). CEST contrast was found to be highly sensitive to phosphorylation on serine residues, intra- and intermolecular disulfide bridge formation, and the binding of negatively charged nucleotides and heparin. In addition, the nucleotide binding constants (Keq) for the protamines were determined through plotting the molar concentration of heparin versus CEST contrast and compared between hPRM1 and salmon protamine. Taken together, these findings are important for explaining the CEST contrast of existing arginine-rich probes as well as serving as a guideline for designing new genetic or synthetic probes.
DOI: 10.1016/j.jconrel.2014.02.005
发表时间: 2014-04-28
期刊: Journal of controlled release : official journal of the Controlled Release Society
影响因子: --
作者:
Chan KW;Yu T;Qiao Y;Liu Q;Yang M;Patel H;Liu G;Kinzler KW;Vogelstein B;Bulte JW;van Zijl PC;Hanes J;Zhou S;McMahon MT
通讯作者: McMahon MT
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发表时间: 2011-08
影响因子: 4.8
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通讯作者: Koretsky AP
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发表时间: 2014-01-17
影响因子: 4
作者:
Bar-Shir, Amnon;Liu, Guanshu;Chan, Kannie W. Y.;Oskolkov, Nikita;Song, Xiaolei;Yadav, Nirbhay N.;Walczak, Piotr;McMahon, Michael T.;van Zijl, Peter C. M.;Bulte, Jeff W. M.;Gilad, Assaf A.
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DOI: 10.1021/ja204701x
发表时间: 2011-10-19
影响因子: 15
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Liu, Guanshu;Liang, Yajie;Bar-Shir, Amnon;Chan, Kannie W. Y.;Galpoththawela, Chulani S.;Bernard, Segun M.;Tse, Terence;Yadav, Nirbhay N.;Walczak, Piotr;McMahon, Michael T.;Bulte, Jeff W. M.;van Zijl, Peter C. M.;Gilad, Assaf A.
通讯作者: Gilad, Assaf A.
DOI: 10.1016/j.jtbi.2005.12.015
发表时间: 2006-08-07
影响因子: 2
作者:
Biegeleisen, Ken
通讯作者: Biegeleisen, Ken