A Fully Synthetic Glycopeptide Antitumor Vaccine Based on Multiple Antigen Presentation on a Hyperbranched Polymer

For antitumor vaccines both the selected tumor‐associated antigen, as well as the mode of its presentation, affect the immune response. According to the principle of multiple antigen presentation, a tumor‐associated MUC1 glycopeptide combined with the immunostimulating T‐cell epitope P2 from tetanus toxoid was coupled to a multi‐functionalized hyperbranched polyglycerol by “click chemistry”. This globular polymeric carrier has a flexible dendrimer‐like structure, which allows optimal antigen presentation to the immune system. The resulting fully synthetic vaccine induced strong immune responses in mice and IgG antibodies recognizing human breast‐cancer cells.     

A Synthetic Glycopeptide Vaccine for the Induction of a Monoclonal Antibody that Differentiates between Normal and Tumor Mammary Cells and Enables the Diagnosis of Human Pancreatic Cancer

In studies within the realm of cancer immunotherapy, the synthesis of exactly specified tumor‐associated glycopeptide antigens is shown to be a key strategy for obtaining a highly selective biological reagent, that is, a monoclonal antibody that completely differentiates between tumor and normal epithelial cells and specifically marks the tumor cells in pancreas tumors. Mucin MUC1, which is overexpressed in many prevalent cancers, was identified as a promising target for this strategy. Tumor‐associated MUC1 differs significantly from that expressed by normal cells, in particular by altered glycosylation. Structurally defined tumor‐associated MUC1 cannot be isolated from tumor cells. We synthesized MUC1–glycopeptide vaccines and analyzed their structure–activity relationships in immunizations; a monoclonal antibody that specifically distinguishes between human normal and tumor epithelial cells was thus generated.     

Syntheses and Immunological Evaluation of Self‐Adjuvanting Clustered N‐Acetyl and N‐Propionyl Sialyl‐Tn Combined with a T‐helper Cell Epitope as Antitumor Vaccine Candidates

Sialyl‐Tn (STn) is a tumor‐associated carbohydrate antigen (TACA) rarely observed on healthy tissues. We synthesized two fully synthetic N‐acetyl and N‐propionyl STn trimer (triSTn) vaccines possessing a T‐helper epitope and a TLR2 agonist, since the clustered STn antigens are highly expressed on many cancer cells. Immunization of both vaccines in mice induced the anti‐triSTn IgG antibodies, which recognized triSTn‐expressing cell lines PANC‐1 and HepG2. The N‐propionyl triSTn vaccine induced the triSTn‐specific IgGs, while IgGs induced by the N‐acetyl triSTn vaccine were less specific. These results illustrated that N‐propionyl triSTn is a valuable unnatural TACA for anticancer vaccines.     

A Facile Synthesis of New Pyrazolo[3,4‐d]pyrimidine Derivatives via a One‐Pot Four‐Component Reaction with Sodium Acetate Supported on Basic Alumina as Promoter

An efficient one‐pot procedure for the synthesis of 3‐amino‐6‐aryl‐2‐phenylpyrazolo[3,4‐d]pyrimidine derivatives, through the reaction of aldehydes, malononitrile, benzamidine hydrochloride, and hydrazine hydrate in the presence of basic alumina‐supported sodium acetate (AcONa/Al₂O₃) under reflux conditions, is reported. This protocol has some advantages, including the use of a simple and one‐pot synthetic approach to attain pyrazolo[3,4‐d]pyrimidine directly from four readily available starting materials, simple workup, high overall yields of the products, and the simultaneous conversion of a NO₂ to an amino group, offering an opportunity to synthesize more complex structures.