Synthesis vaccine

Development of conjugate and peptide vaccines requires the typical organic synthesis process and purification. This is a new area for vaccine technologists. Again, the main concern is to maintain the immunogenicity of the vaccine candidate during the chemical reaction and purification steps. 

S. Dziadek and H. Kunz, Synthesis of tumor-associated glycopeptides antigens for the development of tumor-selective vaccines, Chem. Rec., 3 (2004) 308-321. 

Pozsgay, V. (1998) Synthesis of glycoconjugate vaccines against Shigella dysenteriae type 1. J. Org. Chem. 63, 5983-5999. 

Tam, J.P. (1988) Synthetic peptide vaccine design Synthesis and properties of a high-density multiple antigenic peptide system. Proc. Natl. Acad. Sci. USA 85, 5409-5413. 

An alternative approach to the production of subunit vaccines entails their direct chemical synthesis. Peptides identical in sequence to short stretches of pathogen-derived polypeptide antigens can be easily and economically synthesized. The feasibility of this approach was first verified in the 1960s, when a hexapeptide purified from the enzymatic digest of tobacco mosaic virus was found to confer limited immunological protection against subsequent administration of the intact virus. (The hexapeptide hapten was initially coupled to bovine serum albumin, used as a carrier to ensure an immunological response.)... 

The trichloroacetimidate method has also found wide applications in the synthesis of various complex oligosaccharides. In the course of the development of chemically defined glycoconjugate vaccines against shigellosis, a decasaccharide, corresponding to two consecutive repeating units of the O-specifk polysaccharide of Shigella... 

Comb copolymers, 7 610t Combed yarn, 11 178 Combes synthesis, of quinolines, 21 189 Combicat, 7 387, 392 Combinational libraries, 7 382 characterization, 7 404-405 composition gradient libraries, 7 407 design, 7 399-400 fabrication, 7 414-419 temperature gradient libraries, 7 407—408 thickness gradient libraries, 7 406 Combination electrodes, 14 30 Combination vaccines, 25 504-505 Combinatorial biology, 16 414 Combinatorial biosynthesis, 15 301-302, 305... 

Multivariate curve resolution, 6 54—56 Multivariate linear regression, 6 32—35 Multivariate optical elements (MOE), 6 68 Multiwalled carbon nanotubes (MWCNTs), 77 48, 49 22 720 26 737. See also Carbon nanotubes (CNTs) Multiwall nanotubes (MWNTs) synthesis of, 26 806 Multiwall fullerenes, 12 231 Multiwall nanotubes (MWNTs), 12 232 Multiwall paper bags, 78 11 Multiway analysis, 6 57-63 Multiyear profitability analysis, 9 535-537 Multiyear venture analysis, 0 537-544 sample, 9 542-S44 Mummification, 5 749 Mumps vaccine, 25 490 491 Mumps virus, 3 137 Municipal biosolids, as biomass, 3 684 Municipal distribution, potential for saline water use in, 26 55-56 Municipal effluents, disposal of, 26 54 Municipal landfill leachate, chemicals found in, 25 876t... 

Volume 36 will be dedicated to carbohydrate-based vaccines and to the utilization of the azide functionality in chemical and biological areas of the glycosciences. There are recent reports on interesting applications of azides in this area, and as starting materials for a variety of important bioactive carbohydrates. Hence, the synthesis, reactivity and application of azides in glycomics will also be included in this volume. 

Pauwels, R., van der Straeten, M., Platteau, B., and Bazin, H. (1983) The non-specific enhancement of allergy. In vivo effects of Bordetella pertussis vaccine on IgE synthesis. Allergy. 38, 239-246. 

Reduction is used for carbonyl functionalities [71, 230] such as thioesters [231], amides [232], and carbamates [233], as well as for sulfur [234] and selenium [122] compounds. Recently, the synthesis of a potential carbohydrate vaccine is described via an reduction-oxidation sequence [235]. An efficient solid-phase synthesis of pyrimidine derivatives that involved reduction of the corresponding nitro derivatives was developed by Makara et al. in 2001 (Scheme 3.9) [236]. 

There are five basic sources of pharmaceuticals. By dollar value of products, fermentation is probably the most important, whereas by tonnage, chemical synthesis is dominant. Fermentation is used for antibiotics such as penicillins and tetracyclines. Chemical synthesis provides drugs such as the psychotropics and antihistamines. Animal extracts provide hormones. Biological sources lead to vaccines and serums. Vegetable extracts provide steroids and alkaloids. The top ten pharmaceutical companies in order of revenues are the following Merck, Pfizer, Bristol-Myers Squibb, Johnson ... 

Ragupathi G, Coltart DM, Williams LJ, Koide J, Kagan E, Allen J, Harris C, Glunz PW, Livingston PO, Danishefsky SJ. On the power of chemical synthesis immunological evaluation of models for multiantigenic evaluation of models for multiantigenic carbohydrate-based cancer vaccines. Proc Natl Acad Sci USA 2002 99 13699-13704. 

The latter approach has been followed in our laboratory. For instance, in studies related to the synthesis of potent multivalent sialoside inhibitors of influenza virus hemagglutinin [34], it became of interest to evaluate the immunogenicity of neoglycoproteins containing sialosides as sole immunodominant hapten. To this end, acetochloroneuraminic acid (1) was transformed into allyl glycoside 2 (Scheme 1) which upon reductive ozonolysis afforded aldehyde 3 in excellent overall yields [35], Reductive amination of 3 to bovine serum albumin (BSA) and tetanus toxoid provided immunogenic vaccines from which specific rabbit IgG anti-sialic acid antibodies were obtained [36]. In order... 

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