Muteins of human interleukin-1 that show enhanced bioactivities.

Using recombinant DNA techniques, we have made a series of amino-terminal muteins of human interleukin-1 (IL-1). Two of the muteins demonstrated 4-7-fold increase in bioactivity as compared to that of the native IL-1. The enhanced biological potency coincides with an increase in both receptor binding affinity and in vivo tumor inhibitory activity. By site specific mutagenesis, we have shown that the arginine at the fourth position of IL-1 is one of the key residues in the function of IL-1. Circular dichroism studies of the amino-terminus analogs showed little structural rearrangement. The change in bioactivity might be due to a change in the stability of the muteins, in the side chain interactions with receptors or in the minor change in folding near the receptor binding site.