SYNTHESIS, SOLUTION CONFORMATION AND INTERLEUKIN-6-RELATED ACTIVITIESOF INTERLEUKIN-6 PEPTIDES

Citation
S. Bosze et al., SYNTHESIS, SOLUTION CONFORMATION AND INTERLEUKIN-6-RELATED ACTIVITIESOF INTERLEUKIN-6 PEPTIDES, The journal of peptide research, 52(3), 1998, pp. 216-228
Citations number
63
Categorie Soggetti
Biology
ISSN journal
1397002X
Volume
52
Issue
3
Year of publication
1998
Pages
216 - 228
Database
ISI
SICI code
1397-002X(1998)52:3<216:SSCAIA>2.0.ZU;2-P
Abstract
Interleukin-6 (IL-6) is a member of the cytokine superfamily character ised by a wide variety of biological activities on various cell types. IL-6 exerts pleiotropic activities on hematopoiesis in the immune res ponse and it is the main regulator of acute-phase protein synthesis in liver cells. According to structure-function studies, residues of hel ix A located at the N-terminal part and/or helix D of the C-terminal p art of the protein are involved in the induction of acute-phase respon ses. Two groups of synthetic peptides corresponding to the 18-46 N-ter minal and the 168-185 C-terminal regions of the IL-6 were prepared by solid-phase synthesis to identify structural requirements for inductio n of fibrinogen or complement factor B synthesis. These peptides were characterised by amino acid analysis, analytical reversed-phase high-p erformance liquid chromatography, fast atom bombardment mass spectrome try, and circular dichroism (CD) spectroscopy. CD results showed that under appropriate conditions both 18-46 and 168-185 related peptides a re able to adopt markedly ordered conformation. We demonstrated that e ven octapeptides from the N-terminal part and truncated derivatives of the C-terminal region preserved some tendency to display the CD curve of periodic conformation. The ability of the peptides to induce de no vo synthesis of acute-phase proteins was evaluated by measuring fibrin ogen and complement factor B levels in the supernatants of human HepG2 cells. These results showed that residues 21-34 are critical for elic iting fibrinogen synthesis in the presence or absence of IL-6. In cont rast, the full-length 168-185 peptide is required for the induction of complement factor B response.