Studies of the synthesis, immunology, and cytotoxicity of a cyclic octapeptide corresponding to TNF-alpha-(59-66).
In an attempt to investigate possible binding domains of the tumor necrosis factors (TNF), we have previously synthesized a cyclic hexapeptide corresponding to murine TNF-(127-132) (cTNF-1). In this report, we describe the synthesis and biological activity of another cyclic octapeptide corresponding to human TNF-alpha-(59-66) (cTNF-2). The design of these cyclic peptides is based on their high sequence homology with corresponding fragments of human TNF-alpha or TNF-beta. Similar to cTNF-1, the cyclic octapeptide cTNF-2 displayed low in vitro cytotoxicity against human HeLa and HEP-2 cell lines. The cyclic peptides cTNF-2 and cTNF-1 were then tested for the induction of interleukin-1 (IL-1) production from human peripheral blood mononuclear cells and monocytes in vitro. At low concentrations, the IL-1 levels induced by these cyclic peptides were similar to that of recombinant TNF-alpha. However, the IL-1 production by cTNF-2 stimulation was dose-dependently increased and reached that of a lipopolysaccharide (LPS; 0.1 micrograms/mL) level. These findings suggest that the fragments corresponding to human TNF-alpha-(59-66) and murine TNF-(127-132) may represent certain binding domains of the tumor necrosis factors that elicit IL-1 production.
Sheh
L
L
Department of Chemistry, Tunghai Christian University, Taichung, Taiwan, R.O.C.
Lin
H H
HH
Jeng
K C
KC
Chen
C F
CF
D000595:Amino Acid Sequence; D001665:Binding Sites; D016923:Cell Death / Q000187:drug effects; D003500:Cyclization; D006367:HeLa Cells; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000276:immunology / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry* / Q000494:pharmacology
D007375:Interleukin-1; D009842:Oligopeptides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha