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Complexes of an Alpha Thymosin Derivative with 185/187 Re and 99m Tc: Structural Analysis and Initial Biological Evaluation
Author(s) -
Benaki Dimitra,
Zikos Christos,
Karachaliou ChrysoulaEvangelia,
Tsitsilonis Ourania,
Leondiadis Leondios,
Kalbacher Hubert,
Voelter Wolfgang,
Papadopoulos Minas,
Pirmettis Ioannis,
Pelecanou Maria,
Livaniou Evangelia
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01425.x
Subject(s) - diastereomer , chemistry , thymosin , biodistribution , chelation , high performance liquid chromatography , stereochemistry , molecule , derivative (finance) , alpha (finance) , proton nmr , nuclear magnetic resonance spectroscopy , chromatography , organic chemistry , biochemistry , in vitro , medicine , construct validity , nursing , economics , financial economics , patient satisfaction
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 18 O‐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.