This thesis focuses on the synthesis and vaccine evaluation of the prostate tumor- associated carbohydrate antigen RM2. The author first presents the use of the [1+2+3] one-pot sequential strategy to successfully synthesise the RM2 antigen and its analogues as single stereoisomers in every glycosylation step, producing good yields and stereoselectivity. He then introduces the conjugation of the synthetic RM2 antigen to the carrier protein CRM197 in an average number of 1–10 to create the prostate cancer vaccine candidate, which is combined with α-galactosylceramide C1, its analogue C34, or Alu. The results of the vaccination studies in mice are also described and indicate that the strongest anti-RM2 antigen titer is exhibited when one molecule of diphtheria toxin (DT) is conjugated with an average of 4.7 molecules of RM2 antigen (DT-RM4.7) and adjuvanted with the glycolipid C34. More importantly, the induced mouse antibodies mediate the effective complement-dependent cytotoxicity (CDC) against the prostate cancer cell line LNCap. The study presented in this thesis is the first ever to successfully synthesize this complex glycan molecule. Owing to the steric hindrance of the adjacent sialyl moiety, the introduction of two sialic acid units to the compact and rigid 3,4 di branched galactoside unit is very challenging and the β-selective and efficient glycosylation of the galactosamine moiety at the 4-position of di branched galactose is also problematic.

Developed from a symposium at the Fourth Chemical Congress of North America (202nd National Meeting of the ACS) in New York City, August 1991, chapter-papers present research on topics including how proteins recognize and bind oligosaccharides, synthesis and immunological properties of glycopeptide T-cell determinants, Vibrio cholerae polysaccharide studies, and purification of oligosaccharide antigens by weak affinity chromatography. Annotation copyright by Book News, Inc., Portland, OR

The fundamental science and the latest developments in carbohydrate-based vaccines The relatively new field of glycoimmunology has emerged from the marriage of glycobiology and immunology, in recognition of the important role carbohydrates play as antigenic determinants. Carbohydrate-Based Vaccines and Immunotherapies comprehensively reviews the state of this exciting field, offering a single source for both the fundamental science and the latest developments. With contributions by leading experts, this resource covers the design, synthesis, evaluation, and applications of various carbohydrate-based vaccines, including polysaccharides, neoglycoproteins, and neoglycolipids. The text approaches vaccine design from a chemical and molecular focus, staying in line with current advances. Key topics covered by Carbohydrate-Based Vaccines and Immunotherapies include: Recent developments towards clinically useful vaccines against bacteria, viruses, parasites, and fungi Using adjuvants to improve immunogenicity and/or immunological properties of vaccines Choosing and designing proper adjuvants for specific targets Abnormal carbohydrates expressed by tumors Carbohydrate-based therapeutic cancer vaccines or cancer immunotherapy Clinical trials results for synthetic cancer vaccines Glycoengineering of cell surface carborhydrates and its anticancer applications Using cell surface carbohydrates for disease diagnosis A single, convenient source of state-of-the-art information from leading authorities in the field, Carbohydrate-Based Vaccines and Immunotherapies is an essential reference for organic chemists and biochemists, academic researchers, and other students and professionals involved in vaccine design.

Many pathogens and aberrant malignant cells express unique carbohydrates on their surface representing attractive targets for vaccine design. Considerable progress has recently been made in the identification of novel carbohydrate based vaccines and a large number has reached clinical phase studies. The success of several licensed carbohydrate based vaccines against bacterial pathogens such as Haemophilus influenzae type b, Neisseria meningitidis or Streptococcus pneumoniae demonstrates their great potential. However, the study of anti-carbohydrate antibodies is technically challenging and partly because of low affinities and promiscuous specificity they have not been medically exploited to full potential. The study of antibody specificities and identification of protective carbohydrate epitopes lies at the heart of successful vaccine design. In addition to therapy, antibodies in general serve as diagnostic tools in medical and scientific laboratories. In this setting high affinity and exquisite specificity are important factors for their successful use. “Anticarbohydrate Antibodies – from molecular basis to clinical application” compiles current knowledge on the immunological recognition of carbohydrates by the adaptive immune system from a molecular perspective providing fundamental insight needed for advancing clinically relevant diagnostics and therapeutic applications. Based on significant progress in the fields of glycoimmunology and structural biology in recent years, the book comprehensively reviews the state-of-the-art in defining the key elements of carbohydrate recognition by antibodies, the molecular mimicry of carbohydrate epitopes as well as the molecular features leading to specific and relaxed binding modes. Backed-up by a combination of modern technologies to elucidate structural details of carbohydrate-antibody interactions, biomedically important carbohydrate antigens from viral, bacterial, parasite, insect and tumor cells have been analyzed in in-depth reviews written by well-known experts in the field. Fundamental knowledge of these molecular mechanisms eventually provides a rational basis to improve efficacy of carbohydrate-based vaccines and to further refine diagnostic tools in detection of pathogens and malignant cells.