Chemoenzymatic Synthesis of a MUC1 Glycopeptide Carrying Non-Natural Sialyl TF-β<i>O</i>-Glycan

Tanaka, Eriko; Nakahara, Yuko; Kuroda, Yasuhiro; Kojima, Naoya; Hojo, Hironobu; Nakahara, Yoshiaki

doi:10.1271/bbb.60244

Cited by 7 publications

(4 citation statements)

References 22 publications

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“…In view of this tedious and inefficient protecting group transformation, we decided to refrain from global O-acetylation. Encouraged by literature precedence with regard to the use of benzylated glycosyl amino acids for SPPS [33] and in spite of the expected increase in acid-sensitivity of the resulting conjugate 6, we exchanged only the labile benzylidene acetal for acetyl groups. Thus, upon selective removal [34] of the benzylidene acetal (31, 77 %), followed by O-acetylation (6, 88 %) and careful acidolysis of the tert-butyl ester, the alternative 2'-deoxy-2'-fluoro-TF-gly-copeptide building block 32 was obtained in 47 % yield over three steps.…”

Section: Resultsmentioning

confidence: 99%

Fluorinated Glycosyl Amino Acids for Mucin‐Like Glycopeptide Antigen Analogues

Wagner

Mersch

Hoffmann‐Röder

2010

Chemistry A European J

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The aberrant glycosylation profiles of mucin glycoproteins on epithelial tumour cells represent attractive target structures for the development of immunotherapy against cancer. Mucin-type glycopeptides have been successfully investigated as molecularly defined vaccine prototypes for triggering humoral immunity but are susceptible to rapid in vivo degradation. As a potential means to enhance the bioavailabilities of the antigenic structures, hydrolysis-resistant carbohydrate analogues with fluorine substituents at positions C6, C2' and C6' were synthesised and incorporated into the tandem repeat sequence of the mucin MUC1. The resulting pseudo-glycopeptides can be used to elucidate the effects of chemically modified antibody determinants on metabolic and immunological properties.

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Section: Resultsmentioning

confidence: 99%

Fluorinated Glycosyl Amino Acids for Mucin‐Like Glycopeptide Antigen Analogues

Wagner

Mersch

Hoffmann‐Röder

2010

Chemistry A European J

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“…These segments were then condensed by the thioester method20, 21 to obtain distinctively sialylated glycopeptide 12 . The benzyl protection strategy was also applied to the synthesis of MUC5AC glycopeptide carrying core 8 O ‐glycan22 as well as MUC1 glycopeptide carrying non‐natural sialyl TF‐β O ‐glycan 23…”

Section: O‐glycosylationmentioning

confidence: 99%

Recent progress in the field of glycopeptide synthesis

Hojo

Nakahara

2007

Biopolymers

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Glycosylation is a common post‐translational modification of proteins. Although its significance in biological system is well recognized, approaches to analyze carbohydrate function are limited. This is because of difficulty in obtaining homogeneous glycoproteins from natural sources. Due to the progress of the carbohydrate and peptide chemistry, syntheses of various homogeneous glycopeptides and glycoproteins, which are suitable for biological studies, have been achieved by chemical means. In this review, we briefly summarize recent advances in the field of glycopeptide synthesis after 1999. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 308–324, 2007. This article was originally published online as an accepted preprint. The ‘Published Online’ date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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“…This method has been successfully used for the synthesis of various glycopeptides and glycoproteins. [5][6][7][8][9][10][11][12][13][14][15][16] The benzyl protection strategy for the carbohydrate moiety has several advantages over the more common acetyl protection strategy: (1) the benzyl-protected sugars usually retain higher reactivity during the glycosylation reactions, which is useful for the construction of complex sugar chains; (2) the benzyl groups are stable under the basic conditions used for the Fmoc-SPPS, which is free from side reactions, such as acyl migration from the carbohydrate to the terminal amino group of the growing peptide chain; and (3) the cleavage of the benzyl group does not require the alkaline conditions, such as NaOMe treatment, which have the potential danger of racemization of amino acid residues and β-elimination of the carbohydrate moiety. Instead, the complexity of this method is that a two-step deprotection is required at the end of the Fmoc-SPPS as follows: (1) TFA treatment to deprotect the peptide portion and (2) the Low-TfOH [17] treatment to deprotect the carbohydrate chain.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Fmoc-Thr Unit Carrying Core 1O-Linked Sugar With Acid-SensitiveO-Protecting Group and Its Application to the Synthesis of Glycosylated Peptide Thioester

Asahina

Fujimoto

Suzuki

et al. 2014

Journal of Carbohydrate Chemistry

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Y. Asahina et al.We newly designed and synthesized a 9-fluorenylmethoxycarbonyl (Fmoc)-threonine unit carrying the core 1 O-glycan, which is protected by the 4-methylbenzyl (MBn) group. This protection tactic enabled not only efficient assembly of glycoamino acid derivatives but also one-step deprotection by trifluoroacetic acid (TFA) after the Fmocsolid-phase peptide synthesis (SPPS). The usefulness of this unit was demonstrated by the Fmoc-SPPS of peptide thioester using the N-alkylcysteine (NAC)-assisted thioesterification method. The human interleukin-2 (1-27) sequence was assembled on the NAC resin and the obtained resin was treated with TFA containing cation scavengers to achieve one-step deprotection. The crude peptide was then thioesterified by reacting with an arylthiol to successfully obtain the desired peptide thioester carrying the core 1 O-glycan.

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Chemoenzymatic Synthesis of a MUC1 Glycopeptide Carrying Non-Natural Sialyl TF-βO-Glycan

Cited by 7 publications

References 22 publications

Fluorinated Glycosyl Amino Acids for Mucin‐Like Glycopeptide Antigen Analogues

Fluorinated Glycosyl Amino Acids for Mucin‐Like Glycopeptide Antigen Analogues

Recent progress in the field of glycopeptide synthesis

Synthesis of Fmoc-Thr Unit Carrying Core 1O-Linked Sugar With Acid-SensitiveO-Protecting Group and Its Application to the Synthesis of Glycosylated Peptide Thioester

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