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Abstract #1903

Synthesis of Human Protamine-1 (HPRM1), a Novel CEST Contrast Agent

Nikita Oskolkov1, Kannie W.Y. Chan2, Amnon Bar-Shir2, Peter C.M. van Zijl1, 3, Jeff W.M. Bulte2, 4, Assaf A. Gilad2, 4, Michael T. McMahon1, 3

1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; 2Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States; 3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States; 4Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Baltimore, MD, United States

We have synthesized human protamine-1 (hPRM1), a compound biologically relevant for packing cellular DNA, which is rich in arginine and generates high CEST contrast associated with the exchangeable protons in the guanidyl group. We have also determined how the contrast varies upon binding of hPRM1 to nucleotides, the natural role of this protein, which is relevant to how it might perform in vivo as contrast material. This synthetic approach has resulted in a high yield and retention of the peptides ability to bind DNA, potentially enabling use of hPRM-1 as an alternative to recombinant or naturally occurring protamine.

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Keywords

acid addition agent allow amino analog analyzed anticoagulation applications approximately arginine arginines assisted audience biologically biology bonding bonds bull cell cells cellular charged chemical chemistry class cleavage comparable complexed compound compounds computed confirmed conformation content contrast couplings crude currently custom dense diamagnetic difficulties disulfide domains double drop electrophoresis engineering exchange exchangeable expression features final form formulation fraction future gene generate genes genetic germ good grants heparin human in vivo institute insulin interact interaction intermolecular investigation isolated johns known liberty long mainly make mass medicine microwave model molecular natural naturally novel nuclear nucleotides occurring offsets packing participate peptide peptides percentage peter positively process produces product program promising proposed protect protein proteins proton pulse purification purified purity radiological radiology rare readout reduced reporter resin rich salmon saturation school science scripts section shorter significantly slow solutions spectrometry step strong structural structure studies sulfate suppl synthesis synthesized synthesizer synthetic table target urea vascular years yellow yield zinc