Structural requirements for the biological activity of thymopentin analogs.
Thymopentin, the synthetic pentapeptide Arg-Lys-Asp-Val-Tyr, corresponds to residues 32-36 of the thymic hormone thymopoietin. Thymopentin, like thymopoietin, induces intracellular cGMP elevations in the human T-cell line, CEM. Thymopentin also displaces radiolabeled thymopoietin from a receptor glycoprotein prepared from CEM cells, provided that a nonapeptide corresponding to thymopoietin is added to block thymopoietin binding to an additional binding site. Twenty nine analogs with single position substitutions were synthesized by solid-phase or classical solution synthesis, and are evaluated in these assays. All analogs that were active gave positive effects in both assays. A number of substitutions were tolerated at positions 2, 4, and 5, but there was an absolute requirement for L- or D-Arg at position 1 and L- or D-Asp at position 3 to maintain biological activity.
D000595:Amino Acid Sequence; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D011869:Radioligand Assay; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000378:metabolism; D016305:Thymopentin; D013946:Thymopoietins / Q000138:chemical synthesis / Q000494:pharmacology*; D013951:Thymus Hormones / Q000494:pharmacology*
D006728:Hormones; D010446:Peptide Fragments; D013946:Thymopoietins; D013951:Thymus Hormones; D006152:Cyclic GMP; D016305:Thymopentin