EFFECTS OF SYNTHETIC THYMOSIN-ALPHA-1 AND ITS ANALOGS ON FERTILIZABILITY OF HUMAN SPERM - SEARCH FOR A BIOLOGICALLY-ACTIVE, STABLE EPITOPE

Thymosin-alpha 1 (T alpha 1) and six T alpha 1 analogs were synthesize d to study structure-function relationships and to search for the biol ogically active and stable epitope(s) that would have clinical applica tion in the treatment of male infertility. Four of these analogs were prepared by modification/substitution of N- and C-terminal amino acids of T alpha 1 peptide, and the other two analogs were fragments having only N-16 amino acids (N-terminal) or C-14 amino acids (C-terminal), respectively, of the T alpha 1 peptide. T alpha 1 and these six analog s were tested for their effects on human sperm penetration rates in th e sperm penetration assay (SPA). T alpha 1 significantly (p <.0001) in creased the penetration rates in SPA, with the strongest enhancing eff ect at 0.5 mu g/100 mu L concentration. Of the six analogs tested only two, T alpha 1-Gly-NH2 and T alpha 1-C-14, retained the enhancing eff ects in SPA. None of the analogs decreased the penetration rates or af fected sperm motility compared to control. The enhancing activity resi des primarily in an epitope, the C-terminal 14 amino acids of T alpha 1. However, for maximal effect both N- and C-terminal amino acids (ser ine and asparagine, respectively) have to be intact and unmodified. Th e T alpha 1-Gly-NH2 analog that had its C-terminal protected was as po tent as the intact T alpha 1 peptide. T alpha 1 and this analog may ha ve clinical applications in treatment of male-factor-mediated infertil ity.