Immunomodulatory molecule
L-Glu-L-Trp was isolated from natural calf thymic
peptide complex
Thymalin by reverse-phase high performance liquid chromatography. On the basis of the synthesized
dipeptide a
pharmaceutical was designed containing this compound, which later receives the brand name
Thymogen. The agent activated T-cell differentiation, T-cell recognition of
peptide-MHC complexes, induced changes in intracellular composition of
cyclic nucleotides, and activated neutrophilic chemotaxis and phagocytosis. The effect of
dipeptide on survival, life span and spontaneous
tumor development was studied in female rats. Seventy-six, five-month-old outbred female rats were randomly subdivided into two groups and were subcutaneously injected with 0.2 ml of
normal saline (controls, 32 rats) or with 5 micrograms/rat of the
dipeptide L-Glu-L-Trp, dissolved in 0.2 ml of saline (44 rats), 5 times per week for 12 months. Animals were monitored up to their natural death and all the
tumors discovered were studied microscopically. Mean life span of rats in both groups was similar but that of 10% maximum survived control rats constituted 949 +/- 16.1 days, whereas in the
dipeptide-treated rats this value was 1048 +/- 21.1 days (P < 0.001). Six out of 44 rats treated with the
drug survived over the maximum life span of control rats (965 days). The aging rate indicated as alpha in the Gompertz equation, was 0.0071 days-1 in controls and 0.0041 days-1 in rats exposed to
L-Glu-L-Trp. Total
tumor incidence was 1.5 times lower (P < 0.01), malignant
tumor incidence 1.7 times lower (P < 0.01), and
hematopoietic malignancies (
leukemias and
lymphomas) 3.4 times lower (P < 0.02) in rats exposed to the
dipeptide in comparison with controls. Thus, treatment with
L-Glu-L-Trp delayed aging rate and decreased spontaneous
tumor incidence in rats.