Synthesis of Type-I and Type-II LacNAc-Repeating Oligosaccharides as the Backbones of Tumor-Associated Lewis Antigens.

Riping Phang,Chun-Hung Lin

doi:10.3389/fimmu.2022.858894

Abstract

Type-I and Type-II LacNAc are Gal-GlcNAc disaccharides bearing a β1,3- or β1,4-linkage respectively. They exist as the backbones of Lewis antigens that are highly expressed in several cancers. Owing to the promise of developing carbohydrate-based anti-cancer vaccines, glycan synthesis at a large scale is indeed an important task. Synthesis of Type-I and Type-II tandem repeat oligomers has been hampered by the presence of GlcNAc residues. Particularly, N-protecting group plays a determining role in affecting glycosyl donor’s reactivity and acceptor’s nucleophilicity. This review discusses several representative studies that assembled desirable glycans in an efficient manner, such as chemoselective one-pot synthesis and chemoenzymatic methods. Additionally, we also highlight solutions that have been offered to tackle long-lasting problems, e.g., prevention of the oxazoline formation and change of donor/acceptor reactivity. In retrospect of scientific achievements, we present the current restrictions and remaining challenges in this less explored frontier.

Highlights

Glycobiology has become a burgeoning field in cancer research in the past two decades [1,2,3,4]
Expressed glycans on cancer cells are known as tumor-associated carbohydrate antigens (TACAs), recognized as biomarkers to distinguish between malignant and normal cells [16,17,18,19,20,21,22]
TACA can be classified into two classes: (i) glycoprotein antigens such as Tn, Thomsen-Friedenreich and sialyl-Tn; (ii) glycolipid antigens

Summary

INTRODUCTION

Glycobiology has become a burgeoning field in cancer research in the past two decades [1,2,3,4]. The most reactive thioglycoside reacts with the second most reactive thioglycoside and this process can be repeated by coupling of the resulting product (that serves as the donor) with another thioglycoside (acceptor) in the order of decreasing anomeric reactivity (reducing RRV), elongating glycans from the nonreducing to the reducing end (Scheme 3) With the systematic investigation on the reactivities of thiotoluenyl-linked disaccharide donors and acceptors (shown as RRVs), Lin and coworkers synthesized various tetrasaccharides by performing chemoselective coupling of these glycosyl donors and acceptors in the presence of NIS and TMSOTf (0.2 equiv), as shown in Scheme 10. The idea of RRVD threshold can significantly prevent aglycon transfer, and help to design synthetic procedures for Type-I LacNAc oligosaccharides with satisfying yields

SYNTHESIS OF OTHER RELATED GLYCANS

Findings

CHALLENGES AND FUTURE PERSPECTIVES