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.
Abiko
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T
Kidney Research Laboratory, Sendai, Japan.
Sekino
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H
D000107:Acetylation; D000595:Amino Acid Sequence; D004355:Drug Stability; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013951:Thymus Hormones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D014511:Uremia / Q000276:immunology
D013951:Thymus Hormones; C014859:thymic humoral factor