Short in Vitro Half‐life of Thymopoietin 32–36 Pentapeptide in Human Plasma

Abstract

Thymopoietin32-36 (TPS) is a synthetic pentapeptide that has the biological activity of its parent molecule, the 49 amino acid thymic hormone thymopoietin. Tritiated t h y m~p o i e t i n~~+~ (3 H-TP5) was prepared by reductive tritiation o f dibromotyrosyl-TPS. The stability o f 'H-TPS in human plasma was studied by analyzing samples by thin-layer chromatography at different time points and quantitating the radioactivity associated with TP5 (Arg-Lys-Asp-Val-Tyr) and its tyrosyl-con taining breakdown products (Lys-Asp-VaI-Tyr, Asp-Val-Tyr, Val-Tyr, Tyr). In plasma (but not in saline) the pentapeptide was rapidly degraded (apparent ttIz 30 seconds) with the corresponding appearance of radioactivityassociated with the other tyrosyl-containing reference compounds. These data imply that the pentapeptide, which is active in vivo, may rapidly trigger changes in responsive cells; sustained circulating levels may not be required for activity.

Determination of thymopentin in beagle dog blood by liquid chromatography with tandem mass spectrometry and its application to a preclinical pharmacokinetic study

“…Through TLC studies, Tischio et al. showed that 3 H‐TP‐5 was rapidly cleaved in vitro by proteases present in human plasma, especially for the peptide bond adjacent to Arg and Lys . The ability of protease inhibitors such as EDTA, puromycin, or phenylmethyl sulfonyl fluoride to increase the stability of TP‐5 was evaluated and Meng et al.…”

Novel Insights Into Appropriate Encapsulation Methods for Bioactive Compounds Into Polymers: A Study With Peptides and HDAC Inhibitors

“…In particular in peptide drug development, the latter is a very important aspect, since peptides are degraded quickly by proteases in the blood plasma . It was shown, for example, that the half‐life of peptide drugs such as angiotensin II (Ang II) and thymopentin (TP‐5) is only 16 and 30 s, respectively, while that of gonadotropin‐releasing hormone (GnRH) is marginally longer with 2–4 min . The successful incorporation of peptides into a polymer was demonstrated earlier for a series of tumor antigenic peptides in poly[(lactic acid) ‐co‐ (glycolic acid)] (PLGA)‐based nanoparticles, which induced a significantly stronger antitumor response than the non‐encapsulated peptides .…”

Expression of thymosin α1-thymopentin fusion peptide in Pichia pastoris and its characterization

“…, an immunomodulator, can improve imbalanced immune systems in patients who suffer from a variety of diseases, such as rheumatoid arthritis (Ambrogi et al, 1992), acquired immunodeficiency syndrome (AIDS) (Coppola et al, 1996;Merigan, et al, 1996) and other immune mediated diseases, however, its short half-life in human plasma (30 seconds) (Tischio et al, 1979) limits its clinical application. So far, many ways have been tried to enhance its half-life and activity, e.g.…”