The search for inhibitors of interleukin-1 based on the sequence of interleukin-1 receptor antagonist.
In order to find the low-molecular-weight interleukin-1 (IL-1) inhibitors, we synthesised a series of peptides, derived from three regions of interleukin-1 receptor antagonist (IL-1ra): N-terminal (residues 5-9), central (90-98) and C-terminal (143-148). The decision was based on the thorough analysis of structural and functional properties of IL-1 proteins and the resemblance of some fragments of IL-1ra to well-known immunomodulators, like thymopentin and tuftsin. The competition between our peptides and IL-1 were measured as the inhibition of IL-1 induced IL-2 production in LBRM/CTLL cell line system. All peptides presented some activity, although the most interesting results (when the range of activity and dose-dependence were taken into account) were obtained for tuftsin and peptide VTKFYF from the C-terminal part of IL-1ra.
Wieczorek
Z
Z
Institute of Immunology and Experimental Therapy, Wroclaw.
Kluczyk
A
A
Slon-Usakiewicz
J J
JJ
Siemion
I Z
IZ
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008958:Models, Molecular; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D014405:Tuftsin / Q000737:chemistry / Q000494:pharmacology
C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007376:Interleukin-2; D010446:Peptide Fragments; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014405:Tuftsin