Hidden Bibliographic Details
ISBN: | 9783662468487 3662468484 9783662468470 3662468476 9783662468470
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Notes: | "Doctoral thesis accepted by National Taiwan University, Taipei, Taiwan." Includes bibliographical references. Online resource; title from PDF title page (Ebsco, viewed May 1, 2015).
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Summary: | 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 1ℓ́ℓ10 to create the prostate cancer vaccine candidate, which is combined with ℓł-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 dibranched galactoside unit is very challenging and the ℓø-selective and efficient glycosylation of the galactosamine moiety at the 4-position of dibranched galactose is also problematic.
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Other form: | Printed edition: 9783662468470
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Standard no.: | 10.1007/978-3-662-46848-7
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