Antibody recognition of fluorinated MUC1 glycopeptide antigens

Abstract

The syntheses of various fluorinated MUC1 glycopeptide antigens and their specific binding to serum antibodies from mice immunized with natural and fluorinated TF(6)-MUC1-TTox conjugate vaccines are presented.

Chemoenzymatic synthesis of mono- and di-fluorinated Thomsen–Friedenreich (T) antigens and their sialylated derivatives

“…14–17 They have been conjugated to tetanus toxoid carrier protein and the conjugate vaccines elicited strong and specific immune responses in mice. 18–19 These “foreign” fluorinated TACA-based vaccines not only provided enhanced immunogenicity and metabolic stability but also improved bioavailability. Despite the broad application of fluorine substitution in medicinal chemistry for generating several blockbuster drugs in the market (such as Lipitor ™ and Prozac ™ , etc.…”

A Cancer Therapeutic Vaccine based on Clustered Tn‐Antigen Mimetics Induces Strong Antibody‐Mediated Protective Immunity

“…[21] One reason for these failures is the sensitivity of TACAs to endogenous glycosidases, which reduces their in vivo bioavailability. [22][23][24] As a consequence, structural modifications to native TACAs, including the use of C-and S-glycosides, [25][26][27] deoxyfluoroglycosides, [28][29][30] truncated antigens, [31] or thioether-bridged mimetics, [32] have been proposed to provide structures more stable than those of the parent antigens without interfering with their B-cell immunogenicity. [33,34] In this study, we hypothesized that TACA-based vaccines displaying mimetics instead of native Tn antigens could be more resistant to enzymatic degradation.…”

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

“…This example clearly suggests that increasing the polar hydrophobicity may help improve biological activity. Furthermore, the group of Hoffmann–Röder made a significant contribution in the preparation of various fluorinated MUC1 glycopeptide antigens, along with the preparation of the corresponding conjugate vaccines . Trifluorinated Thomsen–Friedenreich (TF) analogue 5 was used in immunization studies and binding experiments with antiserum obtained from immunization with a conjugate vaccine carrying the TF antigen glycan.…”

“…[11] This example clearly suggests that increasing the polar hydrophobicity mayh elp improve biological activity.F urthermore, the group of Hoffmann-Rçder made as ignificant contribution in the preparation of various fluorinated MUC1 glycopeptide antigens, [12] along with the preparation of the correspondingc onjugate vaccines. [13] Trifluorinated Thomsen-Friedenreich (TF) analogue 5 was used in immunization studies and binding experimentsw ith antiserum obtained from immunizationw ith ac onjugate vaccine carrying the TF antigen glycan.T he antisera derived from fluoroglycoconjugates showeds mall differences in binding to the fluorinated antigens. This work showed that fluorinated tumora ssociated carbohydrate antigensc ould be used for the design of vaccines with enhanced metabolic stability.…”