24 新規結合型糖ペプチドの全合成 : C-結合型糖ペプチド(口頭発表の部)

抄録

It is now widely recognized that attachment of carbohydrate is one of the most important posttranslational modifications which affects their biological activities by way of controlling higher order structure, stability, immunogenicity, and carbohydrate-protein interaction. In most cases, protein glycosylation can be classified into two major subtypes: O-glycosylation, where an N-acetylgalactosamine residue is linked to the hydroxyl group of either serine or threonine, and N-glycosylation, where a glycan chain is linked via a glycosylamido linkage to an asparagine residue. However, in 1994, a new class of glycoprotein structural motif was identified in human RNase, where a mannose residue is connected to tryptophan via a C-glycosidic linkage. More recently, the same structural motif was found from recombinant human IL12. The total synthesis of this novel type of glyco-amino acid, C^2-α-L-C-mannosylpyranosyl-L-tryptophan has been achieved in a stereocontrolled manner. Mannose moiety and (L)-tryptophanol derivative were connected via epoxide opening reaction. After several functional group transformation, the target molecule was synthesized in a concise manner. With rigorously defined synthetic molecule in hand, ^1H NMR analysis cleanly revealed that mannosylated tryptophan itself adopts the ^1C_4 conformation with the equatorially oriented tryptophan moiety. Peptide elongation reaction was also accomplished by using intermediate azide acid in solution phase. By use of tetramethylfluoroformidium hexafluorophosphate, coupling with tripeptide was achieved in high yield. After selective reduction of azide at N-termini, further peptide elongation was successfully performed to afford the protected hexapeptide sequence, which corresponds to the partial structure of human RNase.