Synthesis of Fluorinated Glycosyl Amino Acid Building Blocks for MUC1 Cancer Vaccine Candidates by Microreactor-Assisted Glycosylation

Abstract

MUC1-type glycopeptides have already shown their potential as possible cancer vaccine candidates. In addition, first examples of fluorinated antigen structures, especially containing the Thomsen-Friedenreich antigen, with similar antibody recognition have been reported. Using microreactor techniques for improvement of the crucial step, the complex glycosylation reactions, is an efficient way to find optimized reaction parameter as well as to circumvent well-known scale-up drawbacks. Besides, this is the first report of continuous flow glycosylations of glycosyl amino acids, in particular with fluorinated glycosyl building blocks.

Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines

“…Some MUC1 glycopeptides with deoxyfluoro TACAs, in which a hydroxyl group in the sugar moiety was substituted by fluorine, were explored as anticancer vaccines with promising antibody titers. [8][9][10][11][12][13] Recently, our group identified some N-acetyl modified STn antigens eliciting stronger immune responses than the native STn antigen. 14 The modified STn conjugates elicited a higher titer of antibodies which could recognize the native STn antigen.…”

Exploring the Chemistry of Non‐sticky Sugars: Synthesis of Polyfluorinated Carbohydrate Analogues of d‐Allopyranose

“…The amine linker will allow future conjugation reactions to carrier proteins with the aim of unveiling novel immunological properties. It is important to point out that the preparation of such fluorinated immunogenic tools is highly challenging and a flow procedure was developed to allow a scale‐up synthesis of fluorinated antigens . Finally, the groups of Diercks and Gabius prepared a fluoro‐ N ‐glycan core trimannoside 7 .…”

“…It is important to point out that the preparation of such fluorinated immunogenic tools is highly challenging and af low procedure was developed to allow as cale-up synthesis of fluorinated antigens. [15] Finally,t he groups of Diercks and Gabius prepared af luoro-N-glycanc ore trimannoside 7. [16] Its recognition to Pisum sativum was confirmed to be via the two terminal mannoser esidues.E xamples presentedi nF igure1 strongly suggest that more research should be directed toward the development of new strategies for the design of fluorinated carbohydratemimetics.…”

Homogeneous Gold-Catalyzed Glycosylations in Continuous Flow

“…An improved method allowing for complex oligosaccharide synthesis replaced the propargylic leaving group with ortho -hexynylbenzoates via gold­(I)-activation. − Initial results using a gold-catalysis protocol proved to be both mild and versatile . The development of reliable glycosylating protocol using mild conditions would be beneficial for oligosaccharide synthesis on solid support − or by flow chemistry. − …”