Synthesis of an immunologically active analog of thymic humoral factor-gamma 2 with enhanced enzymatic stability

Acetyl-thymic humoral factor-gamma 2 chloromethyl ketone [Ac-Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu-CH2Cl], an analog of thymic humoral factor-gamma 2, was synthesized and studied for its immunological effects on the impaired blastogenic response of T-lymphocytes isolated from uremic patients. Synthetic thymic humoral factor-gamma 2 and the synthetic acetyl-thymic humoral factor-gamma 2 chloromethyl ketone both restored the impaired blastogenic response of T-lymphocytes of uremic patients. However, the synthetic thymic humoral factor-gamma 2 is susceptible to proteolytic digestion. On the other hand, the synthetic acetylthymic humoral factor-gamma 2 chloromethyl ketone retained activity and was shown to exhibit a high degree of stability when incubated in human serum, These results indicate that N-terminal acetylation and the introduction of a chloromethyl ketone residue into the C-terminal residue of thymic humoral factor-gamma 2 increase resistance to proteolytic degradation by exopeptidases without loss of immunological activity.