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Conformational perturbation of interleukin‐2: A strategy for the design of cytokine analogs
Author(s) -
Landgraf Bryan E.,
Williams Diane P.,
Murphy John R.,
Smith Kendall A.,
Ciardelli Thomas L.
Publication year - 1991
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.340090306
Subject(s) - cytokine , interleukin 4 , chemistry , computational biology , immunology , biology
Interleukin‐2 (IL‐2) is a representative of a growing family of small proteins termed lymphokines which are responsible for mediating cell differentiation, growth and function in the immune system. Many of these proteins are being evaluated for their clinical potential. From the perspective of drug development, structure–function analysis of these molecules and their receptors require the use methodologies different than those traditionally employed for small peptides and other natural products. However, similar pharmacologic principles apply and an understanding of ligand‐receptor interactions and the asssociated responses is required in order to efficiently pursue agonist and antagonist design. Although IL‐2 is a protein of only 133 amino acid residues for which a low resolution X‐ray structure does exist, the complexity of its receptor system has provided an added challenge to structure–function studies. Consequently, little is known concerning the receptor contact residues for this protein. We have attempted to utilize established principles of protein and peptide structure to manipulate the conformation of IL‐2 in a manner which has provided analogs helpful for receptor interactions studies. These proteins have not only providing useful information on the nature of the IL‐2 receptor but have also revealed potential strategies for the design of IL‐2 agonists and antagonists.