Preclinical validation of the heparin-reactive peptide p5+14 as a molecular imaging agent for visceral amyloidosis

Jonathan Wall, Emily Martin, Tina Richey, Alan C. Stuckey, Sallie Macy, Craig Wooliver, Angela Williams, James S. Foster, Penney McWilliams-Koeppen, Ed Uberbacher, Xiaolin Cheng, Stephen Kennel

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)7657-7682
Number of pages26
JournalMolecules
Volume20
Issue number5
DOIs
StatePublished - May 1 2015

Fingerprint

heparins
Molecular imaging
Molecular Imaging
Amyloidosis
Amyloid
peptides
Heparin
Peptides
sulfation
proteins
Glycosaminoglycans
sulfates
deposits
Tissue
Amyloidogenic Proteins
Heparan Sulfate Proteoglycans
peptide p5 plus 14
Amyloid Plaques
Medical imaging
matrices

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Preclinical validation of the heparin-reactive peptide p5+14 as a molecular imaging agent for visceral amyloidosis. / Wall, Jonathan; Martin, Emily; Richey, Tina; Stuckey, Alan C.; Macy, Sallie; Wooliver, Craig; Williams, Angela; Foster, James S.; McWilliams-Koeppen, Penney; Uberbacher, Ed; Cheng, Xiaolin; Kennel, Stephen.

In: Molecules, Vol. 20, No. 5, 01.05.2015, p. 7657-7682.

Research output: Contribution to journalArticle

Wall, J, Martin, E, Richey, T, Stuckey, AC, Macy, S, Wooliver, C, Williams, A, Foster, JS, McWilliams-Koeppen, P, Uberbacher, E, Cheng, X & Kennel, S 2015, 'Preclinical validation of the heparin-reactive peptide p5+14 as a molecular imaging agent for visceral amyloidosis', Molecules, vol. 20, no. 5, pp. 7657-7682. https://doi.org/10.3390/molecules20057657
Wall, Jonathan ; Martin, Emily ; Richey, Tina ; Stuckey, Alan C. ; Macy, Sallie ; Wooliver, Craig ; Williams, Angela ; Foster, James S. ; McWilliams-Koeppen, Penney ; Uberbacher, Ed ; Cheng, Xiaolin ; Kennel, Stephen. / Preclinical validation of the heparin-reactive peptide p5+14 as a molecular imaging agent for visceral amyloidosis. In: Molecules. 2015 ; Vol. 20, No. 5. pp. 7657-7682.
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