抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

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The Huisgen 1,3-dipolar cycloaddition reaction of organic azides and alkynes has gained considerable attention in recent years due to the introduction in 2001 of Cu(1) catalysis by Tornoe and Meldal, leading to a major improvement in both rate and regioselectivity of the reaction, as realized independently by the Meldal and the Sharpless laboratories. The great success of the Cu(1) catalyzed reaction is rooted in the fact that it is a virtually quantitative, very robust, insensitive, general, and orthogonal ligation reaction, suitable for even biomolecular ligation and in vivo tagging or as a polymerization reaction for synthesis of long linear polymers. The triazole formed is essentially chemically inert to reactive conditions, e.g. oxidation, reduction, and hydrolysis, and has an intermediate polarity with a dipolar moment of ∼5 D. The basis for the unique properties and rate enhancement for triazole formation under Cu(1) catalysis should be found in the high ∆G of the reaction in combination with the low character of polarity of the dipole of the noncatalyzed thermal reaction, which leads to a considerable activation barrier. In order to understand the reaction in detail, it therefore seems important to spend a moment to consider the structural and mechanistic aspects of the catalysis. The reaction is quite insensitive to reaction conditions as long as Cu(1) is present and may be performed in an aqueous or organic environment both in solution and on solid support.

Cu-catalyzed azide-alkyne cycloaddition.

In studying the evolution of organic chemistry and grasping its essence, one comes quickly to the conclusion that no other type of reaction plays as large a role in shaping this domain of science than carbon-carbon bond-forming reactions. The Grignard, Diels-Alder, and Wittig reactions are but three prominent examples of such processes, and are among those which have undeniably exercised decisive roles in the last century in the emergence of chemical synthesis as we know it today. In the last quarter of the 20th century, a new family of carbon-carbon bond-forming reactions based on transition-metal catalysts evolved as powerful tools in synthesis. Among them, the palladium-catalyzed cross-coupling reactions are the most prominent. In this Review, highlights of a number of selected syntheses are discussed. The examples chosen demonstrate the enormous power of these processes in the art of total synthesis and underscore their future potential in chemical synthesis.

Palladium-catalyzed cross-coupling reactions in total synthesis.

The cluster glycoside effect.

Sugar amino acids (SAAs), which are carbohydrate derivatives with both an amino group and a carboxyl group connected to the carbohydrate frame, have found wide application as building blocks for oligosaccharide and peptide mimetics, as secondary-structure inducing elements, and as pharmacophore-presenting scaffolds for the generation of combinatorial libraries. Used as monomers with a rigid pyran ring, functional pharmacophoric groups attached to the hydroxy, amino, and carboxyl groups can be presented in a distinct spatial arrangement as was demonstrated in seminal studies by Hirschmann et al. Linear and cyclic oligomers of SAAs have been synthesized, taking advantage of well-established peptide chemistry, and in certain cases they adopt defined secondary structures. Sugar amino acids with an additional amino group, that is, sugar diamino acids, would be an attractive extension of this concept, giving access to novel branched oligomeric structures. However, their synthesis has not been reported until now. Here we introduce the protected derivatives 1 and 2 of 2,6-diamino-2,6-dideoxy-b-d-glucopyranosyl carboxylic acid,

/pdf/orthogonally-protected-sugar-diamino-acids-as-building-3cd3rvl2o6.pdf

Orthogonally Protected Sugar Diamino Acids as Building Blocks for Linear and Branched Oligosaccharide Mimetics

https://kops.uni-konstanz.de/bitstream/handle/123456789/9830/witt_039.pdf;sequence=1

Probing multivalent carbohydrate-lectin interactions by an enzyme-linked lectin assay employing covalently immobilized carbohydrates.

8: Boc-Lys(Aloc)-Orn(Ddv)-Gly-Ala-D-Lys(Ddv)-Orn(Ddv)-D-Val-Glu(OAll)-Bal-Sieber-TG (0.54 g, 70 μmol) was shaken for 16 h under argon with morpholine (77 μl, 0.88 mmol) and Pd(PPh3)4 (12 mg, 10 μmol) in DMF/DMSO (1:1) (3 mL) and subsequently washed with DMF and CH2Cl2. After treatment of a resin sample with the cleavage cocktail, remaining 8 was extracted with MeOH from the solid support. HPLC (20–80 % acetonitrile in water/0.1 % TFA over 30 min): retention time tR = 18.5 min; ESI-MS (M + H ): calcd. 1648.0, found 1648.6.

/pdf/combinatorial-solid-phase-synthesis-of-multivalent-cyclic-4r1eiztt5h.pdf

Combinatorial Solid-Phase Synthesis of Multivalent Cyclic Neoglycopeptides.

https://pubs.rsc.org/en/content/articlepdf/2014/cc/c4cc04332d?page=search

Efficient labelling of enzymatically synthesized vinyl-modified DNA by an inverse-electron-demand Diels–Alder reaction

Carbohydrate microarrays are an emerging tool for the high-throughput screening of carbohydrate–protein interactions that represent the basis of many biologically and medicinally relevant processes. The crucial step in the preparation of carbohydrate arrays is the attachment of carbohydrate probes to the surface. We examined the Diels–Alder reaction with inverse-electron-demand (DARinv) as an irreversible, chemoselective ligation reaction for that purpose. After having shown the efficiency of the DARinv in solution, we prepared a series of carbohydrate–dienophile conjugates that were printed onto tetrazine-modified glass slides. Binding experiments with fluorescently labeled lectins proved successful and homogeneous immobilization was achieved by the DARinv. For immobilization of nonfunctionalized reducing oligosaccharides we developed a bifunctional chemoselective linker that enabled the attachment of a dienophile tag to the oligosaccharides through oxime ligation. The conjugates obtained were successfully immobilized on glass slides. The presented strategies for the immobilization of both synthetic carbohydrate derivatives and unprotected reducing oligosaccharides facilitate the preparation of high-quality carbohydrate microarrays by means of the chemoselective DARinv. This concept can be readily adapted for the preparation of other biomolecule arrays.

/pdf/preparation-of-carbohydrate-arrays-by-using-diels-alder-496ypha94r.pdf

Valentin Wittmann

Papers

Orthogonally Protected Sugar Diamino Acids as Building Blocks for Linear and Branched Oligosaccharide Mimetics

Probing multivalent carbohydrate-lectin interactions by an enzyme-linked lectin assay employing covalently immobilized carbohydrates.

Combinatorial Solid-Phase Synthesis of Multivalent Cyclic Neoglycopeptides.

Efficient labelling of enzymatically synthesized vinyl-modified DNA by an inverse-electron-demand Diels–Alder reaction

Preparation of Carbohydrate Arrays by Using Diels–Alder Reactions with Inverse Electron Demand