title: Albumin-binding PARACEST agents.
abstract: Lanthanide complexes (Eu(3+), Gd(3+) and Yb(3+)) 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 Eu(3+)-bound water molecule, making these PARACEST complexes potentially useful as vascular MRI agents. Yb2 also showed a detectable CEST effect from both the Yb(3+)-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 microM, 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.
authors.affiliation: Department of Chemistry, University of Texas at Dallas, P.O. Box 830688, Richardson, TX 75083-0688, USA.
authors.forename: M Meser
authors.initials: MM
authors.lastname: Ali
authors.forename: Mark
authors.initials: M
authors.lastname: Woods
authors.forename: Eul Hyun
authors.initials: EH
authors.lastname: Suh
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kovacs
authors.forename: Gyula
authors.initials: G
authors.lastname: Tircsó
authors.forename: Piyu
authors.initials: P
authors.lastname: Zhao
authors.forename: Vikram D
authors.initials: VD
authors.lastname: Kodibagkar
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
mesh_terms: D001665:Binding Sites; D006801:Humans; D028581:Lanthanoid Series Elements / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D014859:Warfarin; D014867:Water
chemical_list: D028581:Lanthanoid Series Elements; D009942:Organometallic Compounds; D012709:Serum Albumin; D014867:Water; D014859:Warfarin