TY - JOUR
T1 - Albumin-binding PARACEST agents
AU - Ali, M. Meser
AU - Woods, Mark
AU - Suh, Eul Hyun
AU - Kovacs, Zoltan
AU - Tircsó, Gyula
AU - Zhao, Piyu
AU - Kodibagkar, Vikram D.
AU - Sherry, A. Dean
N1 - Funding Information:
Acknowledgements This research was supported in part by grants from the National Institutes of Health (CA-115531, DK-058398, EB-04285, and RR-02584), the Department of Defense Breast Cancer Research Program (Idea grant W81XWH-05-1-0223), and the Robert A. Welch Foundation (AT-584).
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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.
KW - Albumin binding
KW - Chemical exchange saturation transfer agents
KW - MRI contrast
KW - Paramagnetic relaxation
UR - http://www.scopus.com/inward/record.url?scp=34547488390&partnerID=8YFLogxK
U2 - 10.1007/s00775-007-0240-z
DO - 10.1007/s00775-007-0240-z
M3 - Article
C2 - 17534672
AN - SCOPUS:34547488390
SN - 0949-8257
VL - 12
SP - 855
EP - 865
JO - Journal of Biological Inorganic Chemistry
JF - Journal of Biological Inorganic Chemistry
IS - 6
ER -