Search

Abstract: Glycopeptide thioester comprising the sequence of extracellular matrix metalloproteinase inducer (emmprin) (34–58) was prepared and condensed with a dendrimer core having eight amino groups by the thioester method. The desired product, a glycopeptide dendrimer carrying an N-linked core pentasaccharide of about 30kDa, was successfully isolated by preparative electrophoresis and characterized by mass analysis. [Copyright &y& Elsevier]

The article discusses the chemoenzymatic synthesis of a mucine-1 (MUC1) glycopeptide carrying non-natural sialyl Thomsen Friedenreich-β Ο-glycan. The synthetic glocopeptide was released from the resin and the resulting benzylated glycopeptide was deprotected under conditions of low-acidity trifluoromethanesulfonic acid. Results show that enzymatic glycosylation was successful with both natural and non-natural Ο-glycans of the synthetic glycopeptide.

The article presents a study which demonstrated the synthesis of a chitobiosylated peptide thioester by the t-butoxycarbonyl strategy. The thioester was used to prepare the peptide sequence derived from extracellular matrix metalloproteinase inducers by the thioester segment condensation method. Circular dichroism spectral measurement characterized the conformation of the glycopeptides.

Studies the solid-phase synthesis of benzyl-protected disaccharide building blocks of core 8 O-glycan protein for glycopeptide by two glycosidation reactions with the glycosyl fluoride method. Separation of the synthetic glycopeptide from the resin with reagent K; Use of the synthetic sample as a suitable standard in studies of the physicochemical or immunochemical characterization of mucin glycoforms.

Abstract: A synthetic method for the core 4 O-glycan-linked Ser and Thr was developed. Highly stereoselective 3-O- and 6-O-glycosylation was achieved by using two distinctively protected N-trichloroacetyllactosaminyl fluorides (3 and 12). Microwave-assisted Zn reduction rapidly and efficiently converted N-trichloroacetylglucosamine (GlcNTCA) to N-acetylglucosamine (GlcNAc). In order to demonstrate the usefulness of the protected core 4 O-glycan a segment (Gly34-Gly58) of emmprin (extracellular matrix metalloproteinase inducer), a cancer metastasis-related glycoprotein, was synthesized by the solid-phase method, utilizing the pentasaccharyl Thr (2) to introduce an O-glycan in place of the native N-glycan at Asn44. [Copyright &y& Elsevier]

The sialylation using sialyl donor with 2,6-dimethylbenzyl (DMBn) ester at C-1 carboxy group rapidly proceeded with good α-selectivity to yield sialyl- N -acetylgalactosaminylated 9-fluorenylmethoxycarbonyl (Fmoc) serine unit. The unit was used for the solid-phase peptide synthesis (SPPS) of the sialyl glycopeptide. The DMBn group was removed during the final deprotection by the trifluoroacetic acid (TFA) treatment keeping the sialyl bond intact and the desired sialyl glycopeptide was successfully obtained. This protecting group strategy provided easier access to sialyl glycoamino acids for sialyl glycopeptides synthesis. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: A novel synthesis of tetralactosaminyl O-glycoamino acid is described. The stereoselective assemblage of a lactosaminyl unit was performed by 2-trichloroacetamido group-assisted β-glycosylation. Initial investigation into the synthesis of decasaccharyl threonine 2 showed limited success because of the low yield in the step concerning the removal of 4-O-chloroacetyl groups. In contrast, 4-O-benzylated decasaccharyl threonine 50 was efficiently synthesized from key LacNAc derivative 35 carrying a 3-O-allyl protecting group at the Gal residue by reiterative glycosylation using the (N-phenyl)trifluoroacetimidate method. Decasaccharide 50 was used as a building block in the solid-phase synthesis of a MUC1-related glycopeptide. Synthetic glycopeptide was obtained through two acidic processes: cleavage from resin with reagent K at a lowered temperature and debenzylation with a diluted cocktail of low-acidity TfOH. Desired glycopeptide 54 was isolated as the major product, while a series of the saccharide-shortened minor products were generated due to the acid-labile property of the β-GlcNAc glycosidic linkages. [Copyright &y& Elsevier]

Abstract: In this study synthesis of Fmoc-aminoacyl-N-ethyl-S-triphenylmethylcysteine, a new N→S acyl migratory device for the preparation of peptide thioesters by Fmoc solid-phase peptide synthesis (SPPS) is described. Condensation of Fmoc-aminoacyl fluoride and N-ethyl-S-triphenylmethylcysteine allyl ester, readily prepared from known S-triphenylmethylcysteine allyl ester, was efficiently promoted in CH2Cl2 under high-pressure (800MPa). When the reaction was performed with the additive DIEA, considerable epimerization at the chiral centers occurred, affording a mixture of diastereomers. When the preparation procedure for N-ethyl-S-triphenylmethylcysteine allyl ester was changed and the additive DIEA in the high-pressure reaction was excluded, Fmoc-aminoacyl-N-ethyl-S-triphenylmethylcysteines was obtained as a single stereoisomer without epimerization. The Fmoc-l-leucine adduct thus prepared was deallylated and used for the SPPS of a known decapeptide. A remarkable increase (44%) in the overall yield of the decapeptidethioester was achieved, compared to the 7% obtained by the stepwise on-resin Leu-Cys condensation method. [Copyright &y& Elsevier]

Abstract: To expand the repertoire of our benzyl-protection strategy for solid-phase glycopeptide synthesis, an O-sulfated glycopeptide was chosen as the synthetic target. Trisaccharyl serine derivatives (Galβ1–4-GlcNAcβ1–2-Manα1–3-Ser) carrying (4-methoxyphenyl)methyl (MPM) groups at either 3-O or 6-O of the Gal residue were prepared through three stereoselective glycosylations. Cleavage of MPM followed by reaction with Me3N·SO3 efficiently afforded 3-O- and 6-O-sulfo-glycoserines, respectively. A preliminary debenzylation study using the sulfated glycoserines revealed that the sulfate groups persisted under ‘low-acidity TfOH’ conditions, when using a limited amount of TfOH and extending the reaction period. The 3-O-sulfo-glycoserine was then introduced into an icosapeptide modeled after an α-dystroglycan fragment by a combination of automated and manual solid-phase peptide synthesis procedures. The synthesized glycopeptide was successfully debenzylated by the low-acidity TfOH cocktail with slight damage to the sulfate functionality. [Copyright &y& Elsevier]

Abstract: In one of the peptide condensation methods termed thioester method, an amino protecting group is required in the lysine side chain. In this study, to investigate the efficiency of the pyruvoyl group as an amino protecting group, we synthesized N α-fluorenylmethoxycarbonyl (Fmoc)-N ε-pyruvoyl-lysine and introduced it into peptides and glycopeptides by the ordinary Fmoc-based solid phase peptide synthesis. The pyruvoyl peptide could be condensed with a peptide thioester by the thioester method, and this protecting group was easily removed by o-phenylenediamine treatment without significant side reactions. [Copyright &y& Elsevier]

Abstract: Core 3 and core 6 O-glycoamino acids were prepared in a protected form suited for Fmoc solid-phase peptide synthesis (SPPS). An N-trichloroacetyllactosamine derivative (2) was used as a highly β-selective glycosyl donor in 3-O-glycosylation of acceptors 3/4 and in 6-O-glycosylation of acceptors 5/6. Zn reduction of trisaccharides 7/8 and 13/14 was followed by acetylation to readily transform trichloroacetamido and azido groups to acetamido groups. Selective deprotection by Pd(0)-catalysis afforded core 3 O-glycan building blocks 11/12 and core 6 O-glycan building blocks 17/18. Usefulness of these building blocks for SPPS was demonstrated by the syntheses of the core 3-linked MUC2 tandem repeat glycopeptide and the core 6-linked glycopeptide segment of MUC6. The synthetic glycopeptides detached from the resin were debenzylated under the ‘low-acidity TfOH’ conditions. [Copyright &y& Elsevier]

The core 2-type tetrasaccharide building blocks (1a/1b) for solid-phase synthesis of glycopeptide were synthesized via stereoselective glycosylation of the disaccharyl Ser/Thr (3a/3b) with a glycosyl fluoride (2) carrying the 2-trichloroacetamido group that was readily converted into a 2-acetamido group by reduction. A segment of glycoprotein leukosialin (215–224) was synthesized by the solid-phase protocol, the building block (1b) being utilized. Cleavage of the synthetic glycopeptide from resin was effected with reagent K and subsequent treatment of the product with a cocktail for the ‘low-acidity TfOH’ facilitated complete removal of the benzyl groups with minimum loss of glycosidic linkages. To the deprotected glycopeptide (21), were enzymatically introduced N-acetylneuraminic acid (sialic acid) residues in remarkably high efficiency by using the specific sialyltransferases. [Copyright &y& Elsevier]