Amino acids labeled with [99mTc(CO)3]+ and recognized by the L-type amino acid transporter LAT1.
We have synthesized amino acids conjugated at the alpha-carbon through an alkyl spacer to a small tripod ligand. The tripod coordinates to the fac-[M(CO)3]+ moiety (M = Re, 99mTc). Depending on the lengths of the spacers, these metal complexes with pendent alpha-amino acids are recognized and transported by the l-type amino acid transporter LAT1. The best result was achieved with a butyl spacer. The Ki value of the corresponding complex is comparable to that of the artificial amino acid BCH. Efflux of [3H]-l-phenylalanine shows that the labeled amino acids do not only bind to the transporter but are transported into the cells. These are the first metal-labeled small molecules which are actively internalized to the intracellular space.
Liu
Yu
Y
Institute of Inorganic Chemistry, University of Zürich, Winterthurerstr. 190, 8057 Zürich, Switzerland.
Pak
Jae Kyoung
JK
Schmutz
Paul
P
Bauwens
Matthias
M
Mertens
John
J
Knight
Hector
H
Alberto
Roger
R
D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism*; D002248:Carbon Monoxide / Q000737:chemistry*; D027283:Large Neutral Amino Acid-Transporter 1 / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013667:Technetium / Q000737:chemistry
D000596:Amino Acids; D027283:Large Neutral Amino Acid-Transporter 1; D013667:Technetium; D002248:Carbon Monoxide