Novel compounds based upon the
thiol N-(carboxy)-beta-alanyl-
cysteamine (vitaletheine) have strikingly potent and seemingly diverse
biological activities. Concentrations of vitaletheine modulators from 1 femtograms/ml to 100 picograms/ml medium regulate RBC production from progenitors initially deprived of
erythropoietin. Similarly, as little as attograms/ml concentrations of the
disulfide vitalethine stimulate immunological responses of murine splenocytes toward sheep RBC in a hemolytic plaque assay. Because dosages of
vitalethine as low as femtograms/kg substantially diminish
tumor size and incidence and increase survival to 80% in mice inoculated with a uniformly fatal
melanoma (Cloudman S-91), activities of these compounds have in vivo significance. A preliminary probe of the benzyl derivative of
vitalethine in a myeloma model (NS-1) suggests efficacy (100% survival) as well. The high potencies of the vitaletheine modulators, both in cell culture and in vivo, indicate that these or similar regulatory components, if constitutively present, probably occur endogenously at vanishingly small concentrations and may be prone to deficiency resulting from metabolic imbalances, irradiation, aging, diet, pathogenic or
parasitic infections, or exposure to
environmental pollutants. Pathways for the biosynthesis of vitaletheine are proposed and chemical syntheses of the vitaletheine modulators are described. Possible molecular mechanisms of action, including interactions with peptidyl
hormones, other endogenous effectors, and
xenobiotic and
pharmaceutical compounds, are explored. Indications for the treatment of other diseases are identified.