Synthesis of an immunologically active fragment analog of prothymosin alpha with enhanced enzymatic stability.
A fragment analog, [D-Arg30]prothymosin alpha fragment 1-30, containing D-arginine in place of arginine residue at position 30 was synthesized by the liquid phase procedure and studied for immunological effect on the impaired blastogenic response of T-lymphocytes isolated from uremic patients after treatment of human serum. Deacetyl-thymosin alpha 1, a synthetic octaeicosapeptide corresponding to deacetyl-prothymosin alpha fragment 1-28, has restoration ability for the impaired blastogenic response of T-lymphocytes of uremic patients but is susceptible to proteolytic digestion. On the other hand, the fragment analog, [D-Arg30]prothymosin alpha fragment 1-30 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 D-residue into the C-terminal residue of prothymosin alpha fragment 1-30 increase resistance to proteolytic degradation by exopeptidases.
Abiko
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T
Kidney Research Laboratory, Sendai, Japan.
Sekino
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H
D000595:Amino Acid Sequence; D004795:Enzyme Stability / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology; D011498:Protein Precursors / Q000138:chemical synthesis* / Q000494:pharmacology; D013947:Thymosin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D010446:Peptide Fragments; D011498:Protein Precursors; C069872:prothymosin alpha (1-30), Arg(30)-; D013947:Thymosin