A catalyCEST MRI contrast agent that detects the enzyme-catalyzed creation of a covalent bond

Dina V. Hingorani, Edward A. Randtke, Mark "Marty" Pagel

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

CatalyCEST MRI can detect enzyme activity by employing contrast agents that are detected through chemical exchange saturation transfer (CEST). A CEST agent, Tm-DO3A-cadaverine, has been designed to detect the catalytic activity of transglutaminase (TGase), which creates a covalent bond between the agent and the side chain of a glutamine amino acid residue. CEST appeared at -9.2 ppm after TGase conjugated Tm-DO3A-cadaverine to albumin, which also caused a decrease in CEST from albumin at +4.6 ppm. Studies with model peptides revealed similar appearances and decreases in detectable CEST effects following TGase-catalyzed conjugation of the contrast agent and peptide. The MR frequencies and amplitudes of these CEST effects were dependent on the peptide sequence, which demonstrated the sensitivity of CEST agents to ligand conformations that may be exploited to create more responsive molecular imaging agents. The chemical exchange rates of the substrates and conjugated products were measured by fitting modified Bloch equations to CEST spectra, which demonstrated that changes in exchange rates can also be used to detect the formation of a covalent bond by catalyCEST MRI.

Original languageEnglish (US)
Pages (from-to)6396-6398
Number of pages3
JournalJournal of the American Chemical Society
Volume135
Issue number17
DOIs
StatePublished - May 1 2013

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Transglutaminases
Covalent bonds
Magnetic resonance imaging
Cadaverine
Contrast Media
Enzymes
Peptides
Albumins
Molecular Imaging
Glutamine
Ligands
Amino Acids
Molecular imaging
Enzyme activity
Conformations
Amino acids
Catalyst activity

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

A catalyCEST MRI contrast agent that detects the enzyme-catalyzed creation of a covalent bond. / Hingorani, Dina V.; Randtke, Edward A.; Pagel, Mark "Marty".

In: Journal of the American Chemical Society, Vol. 135, No. 17, 01.05.2013, p. 6396-6398.

Research output: Contribution to journalArticle

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