Synthesis of peptide-cellulose conjugate mediated by a soluble cellulose derivative having β-Ala esters (II): conjugates with O-phospho-l-serine-containing peptides

A synthetic route is described here for novel peptide-cellulose conjugates containing O-phospho-l-serine. First, Boc-Ser(PO3Ph2) and the related dipeptides, Boc-Ser(PO3Ph2)-Asp(OBzl) and Boc-Asp(OBzl)-Ser(PO3Ph2), were synthesized by adopting the phosphoryl-protection strategy. The condensation reaction between the alpha-carboxyl group of the protected Boc-Ser(PO3Ph2) and the beta-amino groups of beta-Ala-Cellulose using isobutyl chloroformate and N-methylmorpholine yielded the product conjugate, N (beta) -[Boc-Ser(PO3Ph2)]-beta-Ala-Cellulose. The degree of substitution of Boc-Ser(PO3Ph2) towards the beta-amino groups of beta-Ala-Cellulose was estimated as DS (N) = 0.75 (maximum, 1.0). Similar reactions between beta-Ala-Cellulose and two kinds of protected dipeptides, Boc-Asp(OBzl)-Ser(PO3Ph2) and Boc-Ser(PO3Ph2)-Asp(OBzl), gave the corresponding conjugates, and the DS (N) was estimated to be 0.95 and 0.69, respectively. The phenyl, benzyl, and Boc groups were removed in one-pot using the Pt2O catalyst in 50 % trifluoroacetic acid/acetic acid. The P-31-NMR and UV-Visible spectra indicated the complete deprotection without any observable elimination of the phosphorylated peptides.