Albumin-binding PARACEST agents

M. Meser Ali, Mark Woods, Eul Hyun Suh, Zoltan Kovacs, Gyula Tircsó, Piyu Zhao, Vikram D. Kodibagkar, A. Dean Sherry

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Lanthanide complexes (Eu3+, Gd3+ and Yb3+) of two different 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid tetraamide derivatives containing two (2) and four (3) O-benzyl-l-serine amide substituents were synthesized and their chemical exchange saturation transfer (CEST) and relaxometric properties were examined in the presence and absence of human serum albumin (HSA). Both Eu2 and Eu3 display a significant CEST effect from a single slowly exchanging Eu3+-bound water molecule, making these PARACEST complexes potentially useful as vascular MRI agents. Yb2 also showed a detectable CEST effect from both the Yb3+-bound water protons and the exchangeable NH amide protons, making it potentially useful as a vascular pH sensor. Fluorescence displacement studies using reporter molecules indicate that both Gd2 and Gd3 displace dansylsarcosine from site II of HSA with inhibition constants of 32 and 96 μM, respectively, but neither complex significantly displaces warfarin from site I. Water proton relaxation enhancements of 135 and 171% were observed upon binding of Gd2 and Gd3 to HSA, respectively, at 298 K and pH 7.4.

Original languageEnglish
Pages (from-to)855-865
Number of pages11
JournalJournal of Biological Inorganic Chemistry
Volume12
Issue number6
DOIs
Publication statusPublished - Aug 2007

Fingerprint

Serum Albumin
Protons
Albumins
Amides
Blood Vessels
Water
pH sensors
Lanthanoid Series Elements
Molecules
Warfarin
Magnetic resonance imaging
Serine
Fluorescence
Derivatives
dansylsarcosine
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Keywords

  • Albumin binding
  • Chemical exchange saturation transfer agents
  • MRI contrast
  • Paramagnetic relaxation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Ali, M. M., Woods, M., Suh, E. H., Kovacs, Z., Tircsó, G., Zhao, P., ... Sherry, A. D. (2007). Albumin-binding PARACEST agents. Journal of Biological Inorganic Chemistry, 12(6), 855-865. https://doi.org/10.1007/s00775-007-0240-z

Albumin-binding PARACEST agents. / Ali, M. Meser; Woods, Mark; Suh, Eul Hyun; Kovacs, Zoltan; Tircsó, Gyula; Zhao, Piyu; Kodibagkar, Vikram D.; Sherry, A. Dean.

In: Journal of Biological Inorganic Chemistry, Vol. 12, No. 6, 08.2007, p. 855-865.

Research output: Contribution to journalArticle

Ali, MM, Woods, M, Suh, EH, Kovacs, Z, Tircsó, G, Zhao, P, Kodibagkar, VD & Sherry, AD 2007, 'Albumin-binding PARACEST agents', Journal of Biological Inorganic Chemistry, vol. 12, no. 6, pp. 855-865. https://doi.org/10.1007/s00775-007-0240-z
Ali, M. Meser ; Woods, Mark ; Suh, Eul Hyun ; Kovacs, Zoltan ; Tircsó, Gyula ; Zhao, Piyu ; Kodibagkar, Vikram D. ; Sherry, A. Dean. / Albumin-binding PARACEST agents. In: Journal of Biological Inorganic Chemistry. 2007 ; Vol. 12, No. 6. pp. 855-865.
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