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.

Conjugation of a novel histidine derivative to biomolecules and labelling with [99mTc(OH2)3(CO)3]+.

The new histidine derivative 3-[1-[3-(9H-fluoren-9-ylmethoxycarbonylamino)-propyl]-1H-imidazol-4-yl]-2-(3-trimethylsilanyl-ethylcarboxyamino)-propionic acid methyl ester (7) has been prepared via alkylation of the histidine urea derivative (7S)-5,6,7,8-tetrahydro-7-(methoxycarbonyl)-5-oxoimidazo-[1,5-c]-pyrimidine (2) with Fmoc-protected 3-iodopropyl-amine, followed by ring opening with 2-trimethylsilylethanol. After Fmoc cleavage by HNEt2, the histidine amine derivative was coupled to biotin, to the pentapeptide leucine-enkephalin and to Vitamin B12-b-acid by amide formation, employing TBTU as the coupling reagent. In order to make the histidine accessible for labelling, the teoc protecting group was removed by either NBu4F (for the biotin conjugate) or by TFA (for the enkephalin and B12 conjugates).

N(epsilon) functionalization of metal and organic protected L-histidine for a highly efficient, direct labeling of biomolecules with [Tc(OH2)3(CO)3]+.

Two different pathways for the introduction of an acetyl group at N(epsilon ) in a N(alpha), N(delta), and -COO protected histidine to afford N(epsilon)-(CH(2)COOH)-histidine derivative 7 b are presented. The purpose of this study is the coupling of 7 b to amino groups in bioactive molecules such as peptides. After full deprotection of such a bioconjugate, histidine provides three coordination sites which efficiently coordinate to [(99m)Tc(OH(2))(3)(CO)(3)](+) or [Re(OH(2))(3)(CO)(3)](+) in a facial geometry.