Functionalized Silver-Ion-Mediated α-dC/β-dC Hybrid Base Pairs with Exceptional Stability: α-d-5-Iodo-2′-Deoxycytidine and Its Octadiynyl Derivative in Metal DNA

Silver-mediated α-dC–Ag⁺–β-dC hybrid base pairs decorated with 5-iodo- or 5-octadiynyl residues are well accommodated in duplex DNA. A strong T_m increase and favorable thermodynamic data for duplex DNA were observed after addition of silver ions. The phenomenon is particularly obvious when both nucleobases of the base pairs are functionalized. Neither the position of the base pair, nor the type of 5-substituent had a negative influence. On the contrary, functionalization of conventional silver-mediated β-dC–Ag⁺–β-dC homo base pairs showed a negative impact induced by the bulky substituents. To this end, cytosine modified 12-mer oligodeoxynucleotides were prepared by solid-phase synthesis employing new α-anomeric 2′-deoxycytidine phosphoramidites. A multigram scale synthesis was developed for 5-iodo-α-d -2′-deoxycytidine ( 1 ) employing the direct glycosylation of cytosine with Hoffer's α-d -halogenose followed by separation of anomeric DMT nucleosides. Regarding base-pair stability and functionalization silver-mediated α/β-dC hybrid base pairs were found to be superior to β/β-dC homo pairs. According to their extraordinary properties, they might find applications in DNA diagnostics, material science, or nanotechnology.     

乌骨鸡活性肽对体外非酶糖基化的抑制作用

采用正交实验优化了体外非酶糖基化反应体系,体系中加入不同浓度的乌骨鸡活性肽I、Ⅱ37 ℃孵育,同时以肌肽为阳性对照,观察乌骨鸡活性肽对非酶糖基化反应的影响.通过测定预定时间体外非酶糖基化体系的吸光度和荧光值计算乌骨鸡活性肽对非酶糖基化反应的抑制率和对非酶糖基化终产物生成的抑制率.结果表明乌骨鸡活性肽Ⅱ对体外非酶糖基化反应和非酶糖基化终产物的生成均具有较强的抑制作用.     

Synthesis and conformational analysis of novel N(OCH3)-linked disaccharide analogues

N(OMe)-linked disaccharide analogues, isosteric to the corresponding natural disaccharides, have been synthesized by chemoselective assembly of unprotected natural monosaccharides with methyl 6-deoxy-6-methoxyamino-alpha-D-glucopyranoside in an aqueous environment. The coupling reactions were found to be chemo- and stereoselective affording beta-(1-->6) disaccharide mimics when using Glc and GlcNAc; in the case of Gal, the beta-anomer was prevalent (beta:alpha=7:1). An iterative method for the synthesis of linear N(OMe) oligosaccharide analogues was demonstrated, based on the use of an unprotected monosaccharide building block in which an oxime functionality at C-6 is converted during the synthesis into the corresponding methoxyamino group. The conformational analysis of these compounds was carried out by using NMR spectroscopy, ab initio, molecular mechanics, and molecular dynamics methods. Optimized geometries and energies of fourteen conformers for each compound have been calculated at the B3LYP/6-31G* level. Predicted conformational equilibria were compared with the results based on NMR experiments and good agreement was found. It appears that N(OMe)-linked disaccharide analogues exhibit a slightly different conformational behavior to their parent natural disaccharides.     

Synthesis of Urea‐Tethered Disaccharides in Water

A new method for the synthesis of urea‐linked disaccharides in aqueous media has been developed. The key feature of our approach is two strained Steyermark‐type gluco‐ and galactopyranosyl oxazolidinones. Each oxazolidinone is attached to a pyranose ring in a di‐equatorial trans‐annulation framework. Reaction of these oxazolidinones with 4‐aminohexopyranose in water proceeded smoothly to afford the urea‐tethered cellobiose and lactose analogues. The galactose‐type oxazolidinone proved to be more reactive than the glucose‐type, which is explained by the presence of an axial hydroxy group at C4 in the former.     

High throughput screening of O-glycosylation conditions

We report a novel methodology for rapid and quantitative screening of O-glycosylation reactions of application to the analysis of parallel reaction systems. Our system exploits perdeuterated benzyl (Bn-d₇) ether, and stereoselectivity and yield are evaluated by ¹H NMR and MALDI-TOF MS, respectively. This paper summarizes over 240 screenings of 1 → 3 linkage formation between glucose residues targeting the α-isomer in high yield.     

糖肽的固相合成

目前糖肽的固相合成可以分为两种策略：构建单元策略和固相糖基化策略。本文对O-连接和N-连接糖肽固相合成的研究进展进行了综述。     

Assembly of a series of malarial glycosylphosphatidylinositol anchor oligosaccharides

We report an efficient and convergent synthesis of a series of oligosaccharides comprised of the malaria GPI glycan (2a), a promising anti-malaria vaccine candidate currently in preclinical trials and several related oligosaccharide sequences (3-8) that are possible biosynthetic precursors of the malarial GPI. A flexible synthetic strategy is disclosed that relies on a late-stage coupling between oligomannosides of varying length and pseudo-disaccharide glycosyl acceptor 11 to readily access various malarial GPI structures. Phosphorylation was accomplished by mild and efficient H-phosphonate chemistry before the final deprotection was carried out by using sodium in ammonia. The direct connection of a thiol group via a phosphate diester linkage to the inositol moiety provides a handle for easy conjugation of the GPI glycan to carrier proteins, immobilization on carbohydrate microarrays and photo-affinity labels identification. These synthetic oligosaccharides will serve as molecular probes.     

Total Synthesis of Sialylated Glycans Related to Avian and Human Influenza Virus Infection

Human and avian influenza type A viruses bind sialylated pentasaccharides. Herein, the total synthesis of four of these glycans is reported. Efficient sialylations relied on two N‐Troc‐protected (Troc=2,2,2‐trichloroethoxycarbonyl) sialic acid building blocks. The first, a thiophenyl glycoside, readily produced the sialyl‐α(2‐6)galactose disaccharide. Combination of the second building block, a novel glycosyl phosphite, and a benzylidene‐protected galactoside produced the best results for the formation of the sialyl‐α(2‐3)galactose. Two common trisaccharides were assembled by the introduction of glucose, galactose, and glucosamine building blocks followed by selective deprotection. Two sets of pentasaccharides were obtained by the union of two sialylgalactose N‐phenyl trifluoroacetimidate building blocks with the two trisaccharides above. Global deprotection furnished the desired pentasaccharides. The products of these total syntheses are currently employed on the surface of carbohydrate microarrays to detect and type different strains of the influenza virus.     

The Synthesis of Gracillin and Dioscin：TWO Typical Representatives of Spirostanol Glycosides

Two spirostanol saponins(gracillin and dioscin)which have the typical sugar moieties were synthesized facilely by a general approach.     

Glycosylation site analysis of human alpha-1-acid glycoprotein (AGP) by capillary liquid chromatography-electrospray mass spectrometry

A new anionic surfactant (RapiGest SF) was successfully used for site-specific analysis of glycosylation in human alpha-1-acid glycoprotein (AGP). By means of this analytical approach combined with capillary HPLC-mass spectrometry (and tandem mass spectrometry), the N-linked glycosylation pattern of AGP was explored. On the basis of mass matching and MS/MS experiments ca 80 different AGP-derived glycopeptides were identified. Glycosylation shows a markedly different pattern for the various glycosylation sites. At sites I and II, triantennary complex-type oligosaccharides predominate and at sites III, IV and V, tetra-antennary complex-type oligosaccharides predominate. Sites IV and V show the presence of additional N-acetyl lactosamine (Gal-GlcNAc) units (even higher degree of branching and/or longer antennae are also present).