Albumin-binding PARACEST agents.
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.
Ali
M Meser
MM
Department of Chemistry, University of Texas at Dallas, P.O. Box 830688, Richardson, TX 75083-0688, USA.
Woods
Mark
M
Suh
Eul Hyun
EH
Kovacs
Zoltan
Z
Tircsó
Gyula
G
Zhao
Piyu
P
Kodibagkar
Vikram D
VD
Sherry
A Dean
AD
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
D028581:Lanthanoid Series Elements; D009942:Organometallic Compounds; D012709:Serum Albumin; D014867:Water; D014859:Warfarin