Complexes of an alpha thymosin derivative with ¹⁸⁵/¹⁸⁷Re and (⁹⁹m)Tc: structural analysis and initial biological evaluation.

Alpha thymosins are a family of immunostimulating peptides first isolated from thymus gland. In the present work, the structure of the ReO(V)³⁺ complex of an alpha 1 thymosin derivative containing the metal-chelating N,N-dimethylglycyl-L-seryl-L-cysteinyl group was studied with NMR, CD, and ESI. The analysis indicated the existence of two interconverting diastereomers depending on the orientation of the side chain of the chelated Ser syn- or anti- to the oxygen of the ReO(V)³⁺ core. The two diastereomers could be separated on HPLC under a slow gradient showing the ratio of syn/anti to be 3:2, in agreement with the NMR data. The conversion process was shown to involve the coordination of a water molecule to the ReO(V)³⁺ core through the incubation of the complex in ¹⁸O-enriched water and subsequent ESI analysis. HPLC analysis of the analogous radioactive (⁹⁹m)TcO(V)³⁺ complex showed the formation of two isomers in the same syn/anti 3:2 ratio. Biodistribution studies of the (⁹⁹m)TcO(V)³⁺ complex in Swiss albino mice with experimentally induced inflammation showed higher accumulated radioactivity in inflamed tissue compared to normal (ratio of inflamed/control tissue 3.9). (⁹⁹m)Tc-labeled complexes of alpha thymosin derivatives are expected to facilitate research on alpha thymosins and accelerate exploitation of these peptides in immunotherapy protocols.