Synthesis and biological activity of [L‐hydroxyproline] 3 ‐tuftsin analogue and its α‐ or β‐ O ‐D‐glucosylated derivatives
1993; Wiley; Volume: 41; Issue: 1 Linguagem: Inglês
10.1111/j.1399-3011.1993.tb00114.x
ISSN0367-8377
AutoresLaura Biondi, Fernando Filira, Raniero Rocchi, Esther Tzehoval, Mati Fridkin,
Tópico(s)Glycosylation and Glycoproteins Research
ResumoSyntheses are described of the Hyp 3 ‐tuftsin analogue and of its derivatives α‐ or β‐ O ‐glycosylated at the side chain function of the hydroxyproline residue. The carbohydrate‐free tetrapeptide was prepared by reacting Z‐Thr‐Lys(Z)‐OH with H‐Hyp‐Arg(NO 2 )‐OBzl by the mixed anhydride procedure. In the synthesis of the α‐glycosylated analogue the O ‐glycosyl amino acid was incorporated by reacting Boc‐(Glcα+β)Hyp‐OH with H‐Arg(NO 2 )‐OBzl through the same procedure. The α‐glucosylated dipeptide was isolated from the diastereomeric mixture, selectively deblocked, and acylated with Z‐Thr‐Lys(Z)‐OH by the mixed anhydride procedure. In the preparation of the β‐glucosylated analogue the BOP procedure was used for reacting Boc‐[Glc(Ac) 4 β]Hyp‐OH with H‐Arg(NO) 2 ‐OBzl was well as for the final coupling to tetrapeptide. Removal of protecting groups from crude tetrapeptides was achieved by catalytic hydrogenation. Deacetylation of the sugar moiety of the β‐glucosylated tetrapeptide was achieved by treatment with sodium methoxide in methanol. The synthetic compounds were isolated by ion exchange chromatography, and characterized by elemental analysis, amino acid analysis, optical rotation and proton NMR. Their capacity to evoke the release of interleukin 1 from mouse peritoneal macrophages and to modulate immunogenic activity of antigen‐fed cells was evaluated, in comparison with tuftsin and rigin. All of the analogues were found to possess tuftsin‐like activity.
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