Naslov
Isomers od D,L-(adamant-2-yl)-glycyl-L-alanyl-D-isoglutamine induce interferon in human mononuclear cells

Autori
Mažuran, Renata ; Vranešić, Branka ; Ikić-Sutlić, Marina ; Simrak, Danijela ; Tomašić, Jelka

Izvornik
Periodicum biologorum (0031-5362) 98 (1996), 3; 305-310

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
adamantyltripeptides; inducers of interferons; antiviral

Sažetak
Background and purpose: In the search of new immunomodulators which could have also an antiviral activity, a new compound containing adamantyl residue coupled to dipeptide, characteristic for peptidoglycan molecule, was synthesized. Two stereoisomers of such novel adamantyltripeptide, D-(adamant-2-yl)-glycyl-L-alanyl-D-isoglutamine (AdTP1) and L-(adamant-2-yl)-glycyl-L-alanyl-D-isoglutamine (AdTP2) were separated and their in vitro effect on interferon (IFN) production in human mononuclear cells was investigated. Materials and methods: The induction of IFN synthesis was studied by using human mononuclear cells treated with tested adamantylpeptides and/or nonspecific IFN inducers: phytohaemagglutinin (PHA), Concavalin A (ConA), phorbol 12-myristate 13-acetate (PMA) and polyinosinic-polycytidylic acid (poly I:C), respectively. WISH cells were used for bioassay of IFN activity as indicator cells, and vesicular stomatitis virus (VSV) as a challenge virus. Inhibitin of catopathic effect by IFN samples was determined. Characterization of synthetized IFN was performed by neutralization assay using specific antibodies. Results and conclusions: The results have shown that AdTP1 and AdTP2 induced IFN-alpha synthesis. The inducing ability of either isomer alone did not differ, i.e. antiviral titres in culture supernatants were the same both for AdTP1 and AdTP2. However, in combination with standard IFN inducers AdTP1 and AdTP2 influenced the IFN production to the different extent. When mononuclear cells were stimulated with AdTP1 and AdTP2, or with Con A, PMA or poly I:C, higher levels of IFN were induced than with each of those inducers alone, and the effect of AdTP2 might be synergistic, at least in combination with poly I:C. Combination of isomers with PHA induced less IFN than PFA alone, and the obseved inhibition of IFN induction was better pronounced in the presence of AdTP2. The most pronounced difference between isomers was observed in neutralization assays. Namely, AdTP2, combined with standard IFN inducers, converted the production of IFN from alpha to gamma-subtype.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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