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Molecules 2015, 20(5), 7657-7682; doi:10.3390/molecules20057657

Preclinical Validation of the Heparin-Reactive Peptide p5+14 as a Molecular Imaging Agent for Visceral Amyloidosis

1
Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USA
2
Department of and Radiology, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USA
3
Bioscience Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA
4
Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Vito Ferro
Received: 27 February 2015 / Accepted: 22 April 2015 / Published: 27 April 2015
(This article belongs to the Special Issue Glycosaminoglycans and Their Mimetics)
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Abstract

Amyloid is a complex pathologic matrix comprised principally of paracrystalline protein fibrils and heparan sulfate proteoglycans. Systemic amyloid diseases are rare, thus, routine diagnosis is often challenging. The glycosaminoglycans ubiquitously present in amyloid deposits are biochemically and electrochemically distinct from those found in the healthy tissues due to the high degree of sulfation. We have exploited this unique property and evaluated heparin-reactive peptides, such as p5+14, as novel agents for specifically targeting and imaging amyloid. Herein, we demonstrate that radiolabeled p5+14 effectively bound murine AA amyloid in vivo by using molecular imaging. Biotinylated peptide also reacted with the major forms of human amyloid in tissue sections as evidenced immunohistochemically. Furthermore, we have demonstrated that the peptide also binds synthetic amyloid fibrils that lack glycosaminoglycans implying that the dense anionic motif present on heparin is mimicked by the amyloid protein fibril itself. These biochemical and functional data support the translation of radiolabeled peptide p5+14 for the clinical imaging of amyloid in patients. View Full-Text
Keywords: glycosaminoglycans; amyloidosis; peptide; imaging; modeling; SPECT; p5+14 glycosaminoglycans; amyloidosis; peptide; imaging; modeling; SPECT; p5+14
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wall, J.S.; Martin, E.B.; Richey, T.; Stuckey, A.C.; Macy, S.; Wooliver, C.; Williams, A.; Foster, J.S.; McWilliams-Koeppen, P.; Uberbacher, E.; Cheng, X.; Kennel, S.J. Preclinical Validation of the Heparin-Reactive Peptide p5+14 as a Molecular Imaging Agent for Visceral Amyloidosis. Molecules 2015, 20, 7657-7682.

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