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Muteins of human interleukin‐1 that show enhanced bioactivities
Author(s) -
Huang James J.,
Newton Robert C.,
Horuk Richard,
Matthew James B.,
Covington Maryanne,
Pezzella Kathleen,
Lin Yuan
Publication year - 1987
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(87)80307-1
Subject(s) - chemistry , interleukin , interleukin 4 , interleukin 1β , pharmacology , immunology , biology , cytokine
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.