Structural and biologic properties of a human aspartic acid-126 interleukin-2 analog.
Point mutations at position 141 in the murine interleukin-2 (IL-2) sequence have been reported to generate proteins with full antagonist activity on some IL-2-dependent cell lines. To evaluate the potential therapeutic utility of this observation, we have prepared recombinant human IL-2 with a point mutation at the corresponding position (Asp for Gln 126) and examined its structural and biologic properties. This mutation apparently induces minor changes in tertiary conformation accompanied by an increased sensitivity to changes in pH. The biologic activity of this analog is greatly reduced, primarily as a result of decreased affinity to the beta/gamma IL-2 receptor complex; however, it is only weakly antagonistic to the IL-2 response of normal peripheral blood lymphocytes.
Buchli
P
P
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755-3833.
Ciardelli
T
T
D000818:Animals; D001224:Aspartic Acid; D001667:Binding, Competitive; D001681:Biological Assay; D002942:Circular Dichroism; D006801:Humans; D007376:Interleukin-2 / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D001224:Aspartic Acid