PMID- 25642384
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2161-1653 (Print)
IS  - 2161-1653 (Electronic)
IS  - 2161-1653 (Linking)
VI  - 4
IP  - 1
DP  - 2015 Jan 20
TI  - Biophysical Characterization of Human Protamine-1 as a Responsive CEST MR 
      Contrast Agent.
PG  - 34-38
AB  - 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 (K(eq)) 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.
FAU - Oskolkov, Nikita
AU  - Oskolkov N
AD  - Russell H. Morgan Department of Radiology and Radiological Science, The Johns 
      Hopkins University School of Medicine , Baltimore, Maryland United States ; F.M. 
      Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute , 
      Baltimore, Maryland United States.
FAU - Bar-Shir, Amnon
AU  - Bar-Shir A
AD  - Russell H. Morgan Department of Radiology and Radiological Science, The Johns 
      Hopkins University School of Medicine , Baltimore, Maryland United States ; 
      Cellular Imaging Section and Vascular Biology Program, Institute for Cell 
      Engineering , Baltimore, Maryland United States.
FAU - Chan, Kannie W Y
AU  - Chan KW
AD  - Russell H. Morgan Department of Radiology and Radiological Science, The Johns 
      Hopkins University School of Medicine , Baltimore, Maryland United States ; F.M. 
      Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute , 
      Baltimore, Maryland United States ; Cellular Imaging Section and Vascular Biology 
      Program, Institute for Cell Engineering , Baltimore, Maryland United States.
FAU - Song, Xiaolei
AU  - Song X
AD  - Russell H. Morgan Department of Radiology and Radiological Science, The Johns 
      Hopkins University School of Medicine , Baltimore, Maryland United States ; F.M. 
      Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute , 
      Baltimore, Maryland United States.
FAU - van Zijl, Peter C M
AU  - van Zijl PC
AD  - Russell H. Morgan Department of Radiology and Radiological Science, The Johns 
      Hopkins University School of Medicine , Baltimore, Maryland United States ; F.M. 
      Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute , 
      Baltimore, Maryland United States.
FAU - Bulte, Jeff W M
AU  - Bulte JW
AD  - Russell H. Morgan Department of Radiology and Radiological Science, The Johns 
      Hopkins University School of Medicine , Baltimore, Maryland United States ; F.M. 
      Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute , 
      Baltimore, Maryland United States ; Cellular Imaging Section and Vascular Biology 
      Program, Institute for Cell Engineering , Baltimore, Maryland United States.
FAU - Gilad, Assaf A
AU  - Gilad AA
AD  - Russell H. Morgan Department of Radiology and Radiological Science, The Johns 
      Hopkins University School of Medicine , Baltimore, Maryland United States ; F.M. 
      Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute , 
      Baltimore, Maryland United States ; Cellular Imaging Section and Vascular Biology 
      Program, Institute for Cell Engineering , Baltimore, Maryland United States.
FAU - McMahon, Michael T
AU  - McMahon MT
AD  - Russell H. Morgan Department of Radiology and Radiological Science, The Johns 
      Hopkins University School of Medicine , Baltimore, Maryland United States ; F.M. 
      Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute , 
      Baltimore, Maryland United States.
LA  - eng
GR  - R01 EB012590/EB/NIBIB NIH HHS/United States
PT  - Journal Article
DEP - 20141216
PL  - United States
TA  - ACS Macro Lett
JT  - ACS macro letters
JID - 101574672
PMC - PMC4307908
EDAT- 2015/02/03 06:00
MHDA- 2015/02/03 06:01
PMCR- 2015/12/16
CRDT- 2015/02/03 06:00
PHST- 2014/10/27 00:00 [received]
PHST- 2014/12/15 00:00 [accepted]
PHST- 2015/02/03 06:00 [entrez]
PHST- 2015/02/03 06:00 [pubmed]
PHST- 2015/02/03 06:01 [medline]
PHST- 2015/12/16 00:00 [pmc-release]
AID - 10.1021/mz500681y [doi]
PST - ppublish
SO  - ACS Macro Lett. 2015 Jan 20;4(1):34-38. doi: 10.1021/mz500681y. Epub 2014 Dec 16.