Cholesterol transport proteins regulate av ast array of cellular processes including lipid metabolism, vesicular and non-vesicular trafficking,o rganelle contact sites,a nd autophagy.D espite their undoubted importance,t he identification of selective modulators of this class of proteins has been challenging due to the structural similarities in the cholesterol-binding site.H erein we report ag eneral strategy for the identification of selective inhibitors of cholesterol transport proteins via the synthesis of adiverse sterol-inspired compound collection. Fusion of ap rimary sterol fragment to an arrayo f secondary privileged scaffolds led to the identification of potent and selective inhibitors of the cholesterol transport protein Aster-C,w hich displayed as urprising preference for the unnatural-sterol AB-ring stereochemistry and new inhibitors of Aster-A. We propose that this strategy can and should be applied to any therapeutically relevant sterol-binding protein.

Glycomacropeptide (GMP), arising from the cleavage of kappa-casein by chymosin or pepsin, has been correlated with a wide variety of biological activities including immunosuppression capacity, inhibition of pathogen invasion, and induction of satiety. Due to the interest in exploiting such potential of GMP, we aimed at characterizing the immunogenic properties of GMP as an indication of its potential allergenicity. Immunogenicity of kappa-casein and GMP were investigated using 2 animal models based on different routes of immunization: 1) mice immunized intraperitoneally or subcutaneously with either kappa-casein, polymerized GMP, GMP coupled to the immunogenic carrier ovalbumin, or GMP alone; 2) mice coadministered kappa-casein or GMP and cholera toxin. The specific antibody response to GMP was evaluated as well as the antigen-specific T-cell response. The results demonstrated that immunization or feeding with kappa-casein induced GMP-specific antibodies, whereas GMP per se lacked immunogenicity independently of the mode of presentation. The size of the presented form of GMP did not influence its immunogenicity. Because the results showed that GMP did not induce a specific T-cell response, we postulate that GMP lacks the ability to stimulate antigen-specific T cells.

Cholesterol transport proteins regulate av ast array of cellular processes including lipid metabolism, vesicular and non-vesicular trafficking,o rganelle contact sites,a nd autophagy.D espite their undoubted importance,t he identification of selective modulators of this class of proteins has been challenging due to the structural similarities in the cholesterol-binding site.H erein we report ag eneral strategy for the identification of selective inhibitors of cholesterol transport proteins via the synthesis of adiverse sterol-inspired compound collection. Fusion of ap rimary sterol fragment to an arrayo f secondary privileged scaffolds led to the identification of potent and selective inhibitors of the cholesterol transport protein Aster-C,w hich displayed as urprising preference for the unnatural-sterol AB-ring stereochemistry and new inhibitors of Aster-A. We propose that this strategy can and should be applied to any therapeutically relevant sterol-binding protein.

No abstract