Peptides are small polymers of 50 amino acids, situated between organic molecules and proteins. Most peptides perform a biochemical-physical function and are therefore considered as potential drugs. In vivo studies, such as blood-brain barrier transport and medical imaging require sensitive analytical techniques, achieved by using radiolabeled tracers. These peptide tracers are synthesised from the reaction with radioactive sodium iodide, incorporating the iodine in the tyrosine or histidine amino acid residue[1]. However, next to enzymatic degradation, it is reported that deiodination occurs in vitro as well as in vivo [2, 3]. This phenomenon should be taken into account since the deiodinated metabolite(s) can cause the biologic activity.
Therefore, the in vitro stability of different iodinated mouse obestatin derivatives is characterised in the main metabolic compartments: plasma, liver and kidney.
Using LC-UV for quantification, significant differences in the degradation kinetics of the iodinated peptides, arising from both enzymatic proteolysis and deiodination, were found when compared to the native, unmodified peptide. LC-MS/MS analysis demonstrated that the cleavage sites were dependent upon the biological matrix and the location of the amino acid residue incorporating the iodine atom(s). The degrading enzymes were found to target peptide bonds further away from the iodine incorporation, while proteolytic cleavages of nearby peptide bonds were inhibited. Di-iodinated amino acid residue containing peptides were found to be more susceptible to deiodination than the mono-iodinated derivative.
References
[1] J. Nemeth, G. Oroszi, B. Jakab, M. Magyarlaki, Z. Szilvassy, E. Roth, B. Farkas, Journal of Radioanalytical and Nuclear Chemistry 2002, 251, 129.
[2] J. C. Solis-S, P. Villalobos, A. Orozco, C. Valverde-R, Journal of Endocrinology 2004, 181, 385.
[3] E. R. Goldberg, L. A. Cohen, Bioorganic Chemistry 1993, 21, 41
