Acta Pharmacologica Sinica 2008 June; 29 (6): 759-771; doi: 10.1111/j.1745-7254.2008.00791.x

Aim: To study the non-covalent interaction between glutathione and common amino acids.

Methods: In total, 120 heroin-dependent patients participated in the randomized, double-blinded, and placebo-controlled study using l-THP treatment. The participants remained in a ward during a 4-week period of l-THP treatment, followed by 4 weeks of observation after treatment. The patients were followed for 3 months after discharge. Outcome measures are the measured severity of the protracted abstinence withdrawal syndrome (PAWS) and the abstinence rate.

Results: The ESI mass spectra revealed that glutathione could interact easily with Met, Phe, Tyr, Ser, or Ile to form non-covalent complexes. The binding of the complexes was further confirmed by CID experiments in a tandem mass spectrometer as well as UV spectroscopy. Moreover, an improved calculation formula was successfully applied to determine the dissociation constants of glutathione binding to Glu, His, or Gln. Finally, a possible formation mechanism for the complexes of glutathione with amino acids was proposed.

Conclusion: The reduced polypeptide γ-glutathione can interact with each of 8 common amino acids, including Glu, His, and Gln to form non-covalent complexes with different affinity.

Keywords: glutathione; amino acids; non-covalent complexes; electrospray ionization mass spectrometry; dissociation constants