Role of protecting groups in the preparation of thiolate complexes of technetium-99 m using cysteine as a model

Abstract

SummaryAn attempt has been made to develop a suitable protecting group for the thiolate function for 99m Tc binding ligands having such function and which could be deprotected automatically during Tc-chelation without the use of any additional reagents. As a model ligand a simple molecule like l-cysteine was selected. Seven S-protected derivatives of this amino acid were synthesized, radiolabelled with technetium-99 m under a variety of experimental conditions and the yield of the desired chelate was compared to that of 99m Tc-l-cysteine, the authentic standard chelate, by HPLC. The corresponding 99 Tc chelate of cysteine from l-cystine and S-thiomethyl l-cysteine was also prepared. It was found that the 99 Tc chelates exhibited similar retention profiles to those of the corresponding 99m Tc chelates in reverse phase HPLC. The results of the biodistribution studies after 99m Tc chelation were likewise compared to those of 99m Tc-l-cysteine. The effect of probenecid on renal excretion was studied only on the 99m Tc chelate of S-thiomethyl-l-cysteine to determine whether tubular excretion was involved. The results suggest that the S-thiomethyl group could be used as an ideal protective group to mask the high reactivity of thiolate functions attached to different 99m Tc binding ligands.

Insight into the structures of Interleukin-18 systems

“…Disulfide bonds contribute to protein folding and their conformational stabilities as well as their general functions ( Roy et al, 2006 ; Chatterjee Debnath et al, 2010 ; Roy and Luck, 2011 ). 1J0S and 3WO2 have four Cys residues (38, 68, 76 and 127), while none of them forms disulfide bridges ( Yamamoto et al, 2004 ).…”

Synthesis of S‐thiomethyl DMSA and S‐thiomethyl ECD, radiolabelling with technetium‐99m and biological evaluation

“…In our previous work, we have attempted to develop a suitable –SH protecting group for thiolate function, and the S ‐thiomethyl (−SCH 3 ) group was proved to be the most successful in this regard. S ‐thiomethyl protection was well studied in cysteine and l , l ′‐EC; thiomethylated precursor of both the ligands produced the desired technetium chelate in quantitative yield . In the present study, we describe the method of thiol protection during technetium chelation of DMSA and ECD.…”

“…The shelf life of both DMSA and ECD kit can be enhanced by suitable protection of the thiolate functionality. In our ongoing study programme, we already developed S ‐thiomethyl as a novel thiol‐protecting group and used to protect the thiol functionality of l ‐cysteine . We also reported that protection of the thiol function of l , l ′‐ethylene dicysteine ( l , l ′‐EC) by S ‐thiomethylation allows automatic deprotection during 99m Tc chelation without the use of any additional reagents.…”

Synthesis of S‐thiomethyl MAG3, radiolabelling with technetium‐99m and biological evaluation

“…S ‐benzoyl mercaptoacetyltriglycine ( 1 ) was prepared as per the reported method . Methylsulphenyl chloride was prepared by following the procedure described by us . HPLC analysis were performed on a reverse phase C‐18 column (4.6 × 250 mm, particle size 5 µm) fitted to a Waters Associates HPLC system (Waters Corporation, MA, USA).…”

“…In the course of our study, S ‐thiomethyl (–S‐CH 3 ) has been developed as a sulfhydryl protecting group and was well studied on different technetium binding –SH containing ligands, for example, cysteine, L,L′‐EC, Dimercaptosuccinic acid and others . In this study, we report the protection of the thiol function of MAG 3 by S ‐thiomethylation that could be deprotected automatically during technetium‐99m labelling at relatively mild reaction condition.…”