Nonapeptide corresponding to the sequence 27-35 of the mature human IL-2 efficiently competes with rIL-2 for binding to thymocyte receptors [corrected].

Previously it was shown [1] that amino acid substitutions at the region of the first alpha-helix of IL-2 specifically inactivate its reactivity with the intermediate-affinity receptor p70, and mutations in the fifth alpha-helix specifically inactivate the binding to the low-affinity receptor p55. We have synthesized the peptides corresponding to the putative binding site of IL-2 with the intermediate-affinity receptor p70 and found that the nonapeptide corresponding to the sequence 27-35 of the mature IL-2 [2] effectively competes with human rIL-2 for binding to thymocyte receptors. Two types of nonapeptide receptors were revealed: those with Kd1 = 1.84 x 10(-8) M and Kd2 = 1.6 x 10(-7) M. The rIL-2 provides a 100% inhibitory effect on the binding of the 125I-labeled nonapeptide to thymocyte receptors, Ki = 3.5 x 10(-8) M. Low immunoproliferative activity of the peptide allows one to recommend it as a specific antiproliferation drug, IL-2 inhibitor [corrected].

The octapeptide corresponding to the region of the highest homology between alpha-interferon and thymosin-alpha 1 effectively competes with both cytokines for common high-affinity receptors on murine thymocytes.

The octapeptide corresponding to human interferon-alpha 2 (Hu IFN-alpha 2) sequence 131-138 has high affinity to murine thymocyte receptors (Kd = 4.2 x 10(-12) M, about 700 receptors per cell). The peptide receptor binding is inhibited by both Hu rIFN-alpha 2 (Ki = 8.6 x 10(-10) M) and thymosin-alpha 1 (TM-alpha 1) (Ki = 3 x 10(-7) M) as well as by the octapeptide homologous to the TM-alpha 1 sequence 16-23 (Ki = 4.5 x 10(-7) M). The peptide from IFN-alpha 2 (131-138) activates murine thymocyte blast transformation at a concentration of 10(-11) M in the presence of 2.5 micrograms/ml of concanavalin A.