Update and perspectives on congenital disorders of glycosylation.

Defects in nine genes of the N-linked glycosylation pathway cause congenital disorders of glycosylation (CDGs) and serious medical consequences. Although glycobiology is seldom featured in a general medical education, an increasing number of physicians are becoming acquainted with the field because it directly impacts patient diagnosis and care. Medical practice and attitudes will change in the postgenomic era, and glycobiology has an opportunity to be a cornerstone of part of that new perspective. This review of recent developments in the CDG field describes the biochemical and molecular basis of these disorders, describes successful experimental approaches, and points out a few perspectives on current problems. The broad, multisystemic presentations of these patients emphasize that glycobiology is very much a general medical science, cutting across many traditional medical specialties. The glycobiology community is well poised to provide novel perspectives for the dedicated clinicians treating both well-known and emerging human diseases.     

Glycobiology in the cytosol: the bitter side of a sweet world

Progress in glycobiology has undergone explosive growth over the past decade with more of the researchers now realizing the importance of glycan chains in various inter- and intracellular processes. However, there is still an area of glycobiology awaiting exploration. This is especially the case for the field of "glycobiology in the cytosol" which remains rather poorly understood. Yet evidence is accumulating to demonstrate that the glycoconjugates and their recognition molecules (i.e. lectins) are often present in this subcellular compartment.     

国际糖生物学战略布局与研究前沿分析

糖生物学与细胞信号转导、发育、免疫等许多领域相关联,是全面、深入理解生命活动所必需的。本文通过分析各国在糖生物学领域的战略布局,并使用ISI Essential Science Indicators数据库和VOS Viewer软件从定量角度分析国际糖生物学领域的研究前沿,为我国制定糖生物学研究相关战略提供借鉴。     

GlyCosmos门户网站在聚糖科学研究中的功能概述

近年来生物学领域的研究不断达到新高度,聚糖逐渐吸引越来越多科学家的目光,很多研究表明聚糖具有多种生物活性,越来越多的相关科研人员开始关注聚糖在生命过程中的作用及其机制。糖生物学逐渐成为生物学领域的热点学科。对于拟从事糖生物学研究或者刚进入该领域的新人来说,GlyCosmos作为一种全面的、统一的糖科学开放门户网站,其数据免费向大众公开,提供了对聚糖相关数据的访问,包括存储库,糖原、糖蛋白、信号通路和疾病相关的各种数据库及Glycome多种可视化数据库,目前最为前沿和统一的多种标准化多糖表示方法及其他多种功能。该网站是近两年才建成,但目前已被广泛使用也被糖生物学家所熟知。本文就GlyCosmos门户网站中的各项功能进行概述,希望帮助拟从事糖生物学研究的新人更好地了解和利用该网站,对于该网站的学习和理解,会对后续从事聚糖相关研究的研究者起到极大的帮助作用,也使后续研究更加便捷。     

植物糖生物学研究进展

自1988年糖生物学概念提出以来, 国内外科学家在动物、微生物领域取得了大量的研究成果, 但植物糖生物学的研究进展较慢, 目前少见系统的专著或综述。该文围绕植物正常生长时糖信号、逆境时糖信号、糖蛋白及其糖链、重要糖基转移酶及植物凝集素等植物糖生物学的主要问题, 全面阐述植物糖生物学的各个研究分支, 并介绍各领域的最新研究进展。提出了植物糖生物学的概念, 并将其定义为研究植物与糖类互作机制及植物体内糖(糖链与糖分子)结构及生物学功能的科学。     

Gene-Network Analysis Identifies Susceptibility Genes Related to Glycobiology in Autism

The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD), and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD.     

植物糖生物学研究进展

自1988年糖生物学概念提出以来,国内外科学家在动物、微生物领域取得了大量的研究成果,但植物糖生物学的研究进展较慢,目前少见系统的专著或综述。该文围绕植物正常生长时糖信号、逆境时糖信号、糖蛋白及其糖链、重要糖基转移酶及植物凝集素等植物糖生物学的主要问题,全面阐述植物糖生物学的各个研究分支,并介绍各领域的最新研究进展。提出了植物糖生物学的概念,并将其定义为研究植物与糖类互作机制及植物体内糖（糖链与糖分子）结构及生物学功能的科学。     

A "glyconutrient sham"

The discipline of glycobiology contributes to our understanding of human health and disease through research, most of which is published in peer-reviewed scientific journals. Recently, legitimate discoveries in glycobiology have been used as marketing tools to help sell plant extracts termed "glyconutrients." The glyconutrient industry has a worldwide sales force of over half a million people and sells nearly half a billion dollars (USD) of products annually. Here we address the relationship between glyconutrients and glycobiology, and how glyconutrient claims may impact the public and our discipline.     

Blood brothers: carbohydrates in xenotransplantation and cancer immunotherapy

Carbohydrate antigens have a central role in the hyperacute rejection of animal-to-human organ grafts (xenotransplantation) and they are emerging in importance in the immunotherapy of cancer. This article traces the historical origins of the discovery of key carbohydrate antigens and explores the future impact of recent technological advances of the field of glycobiology as it relates to xenotransplantation and cancer.     

Glycopeptides as versatile tools for glycobiology

This review describes the recent advances in the field of glycopeptide and small glycoprotein synthesis. The strategies covered include chemical and chemoenzymatic synthesis, native chemical ligation (NCL), and expressed chemical ligation. The importance of glycopeptide synthesis is exemplified by giving the reader an overview of how versatile and important these well-defined glycopeptides are as tools in glycobiology.     

The history of glycobiology in Japan

This mini review surveys the major accomplishments in the field of glycoconjugates research in Japan, which were made after World War II. It describes early movements in the field of glycoconjugate research in Japan, development of the new techniques to investigate structures of the sugar chains of glycoconjugates, studies of the functions of the sugar chain moieties, and the political movement in Japan to support the basic research necessary for the development of glycotechnology. As introduced in this short article, important groundwork for glycobiology was made by Japanese researchers.     

920 MHz ultra-high field NMR approaches to structural glycobiology

Although NMR spectroscopy has great potential to provide us with detailed structural information on oligosaccharides and glycoconjugates, the carbohydrate NMR analyses have been hampered by the severe spectral overlapping and the insufficiency of the conformational restraints. Recently, ultra-high field NMR spectrometers have become available for applications to structural analyses of biological macromolecules. Here we demonstrate that ultra-high fields offer not only increases in sensitivity and chemical shift dispersion but also potential benefits for providing unique information on chemical exchange and relaxation, by displaying NMR spectral data of oligosaccharide, glycoprotein, and glycolipid systems recorded at a 21.6 T magnetic field (corresponding to 920 MHz ¹H observation frequency). The ultra-high field NMR spectroscopy combined with sugar library and stable-isotope labeling approaches will open new horizons in structural glycobiology.     

N-glycan and Alzheimer's disease

BackgroundAlzheimer's disease (AD) is a major form of dementia. Many evidence-based clinical trials have been performed, but no effective treatment has yet been developed. This suggests that our understanding of AD patho-mechanisms is still insufficient. In particular, the pathological roles of posttranslational modifications including glycosylation have remained poorly understood, but recent advances in glycobiology technology have gradually revealed that sugar modifications of AD-related molecules are profoundly involved in the onset and progression of this disease.Scope of reviewWe summarize the roles of N-glycans in AD pathogenesis and progression, particularly focusing on key AD-related molecules, including amyloid precursor protein (APP), α-, β-, and γ-secretases, and tau.Major conclusionsBiochemical, genetic and pharmacological studies have gradually revealed how N-glycans regulate AD development and progression through functional modulation of the key glycoproteins. These findings suggest that further glycobiology approaches in AD research will reveal novel glycan-based drug targets and early biomarkers of AD. However, N-glycan structures of these molecules in physiological and disease conditions and their precise functions are still largely unclear. Deeper glycobiology studies will be needed to reveal how AD pathology is regulated by glycosylation.General significanceIt is now known that N-glycans play significant roles in AD development. However, specific pathological functions of particular glycan epitopes on each AD-related glycoprotein are still poorly understood. Future glycobiology studies with more sensitive glycoproteomic techniques and a wider variety of chemical glycosylation inhibitors could contribute to the development of novel glycan-based AD therapeutics. This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa.     

硫酸类肝素中的N－非取代葡糖胺残基的功能、结构与生物合成

硫酸类肝素在人类的某些重大疾病如癌症、艾滋病、老年痴呆症中扮演着一些 重要的角色,因而是现今糖类化合物中研究的热门焦点之一.近年的研究表明, 硫酸 类肝素中所含的微量结构,即N－非取代葡萄糖胺残基有着重要的生物学与病理生理学 作用.它与病毒的侵入、脑组织损伤、蛋白聚糖的体内循环等作用密切相关.对硫酸类 肝素中N－非取代葡糖胺残基的结构、功能及其生物体内合成途径的研究将有助于揭 示某些疾病的发病机制,为改善诊断方法和发展药物提供可能.本文综述近10多年来 国内外在该领域的最新研究进展.     

Plant‐insect interactions: what can we learn from plant lectins?

Many plant lectins have high anti‐insect potential. Although the effects of most lectins are only moderately influencing development or population growth of the insect, some lectins have strong insecticidal properties. In addition, some studies report a deterrent activity towards feeding and oviposition behavior. Transmission of plant lectins to the next trophic level has been investigated for several tritrophic interactions. Effects of lectins with different sugar specificities can vary substantially with the insect species under investigation and with the experimental setup. Lectin binding in the insect is an essential step in exerting a toxic effect. Attempts have been made to study the interactions of lectins in several insect tissues and to identify lectin‐binding receptors. Ingested lectins generally bind to parts of the insect gut. Furthermore, some lectins such as the Galanthus nivalus agglutinin (GNA) cross the gut epithelium into the hemolymph and other tissues. Recently, several candidate lectin‐binding receptors have been isolated from midgut extracts. To date little is known about the exact mechanism for insecticidal activity of plant lectins. However, insect glycobiology is an emerging research field and the recent technological advances in the analysis of lectin carbohydrate specificities and insect glycobiology will certainly lead to new insights in the interactions between plant lectins and insects, and to a better understanding of the molecular mechanisms involved. © 2010 Wiley Periodicals, Inc.     

Solid-phase chemical tools for glycobiology

Techniques involving solid supports have played crucial roles in the development of genomics, proteomics, and in molecular biology in general. Similarly, methods for immobilization or attachment to surfaces and resins have become ubiquitous in sequencing, synthesis, analysis, and screening of oligonucleotides, peptides, and proteins. However, solid-phase tools have been employed to a much lesser extent in glycobiology and glycomics. This review provides a comprehensive overview of solid-phase chemical tools for glycobiology including methodologies and applications. We provide a broad perspective of different approaches, including some well-established ones, such as immobilization in microtiter plates and to cross-linked polymers. Emerging areas such as glycan microarrays and glycan sequencing, quantum dots, and gold nanoparticles for nanobioscience applications are also discussed. The applications reviewed here include enzymology, immunology, elucidation of biosynthesis, and systems biology, as well as first steps toward solid-supported sequencing. From these methods and applications emerge a general vision for the use of solid-phase chemical tools in glycobiology.     

920 MHz ultra-high field NMR approaches to structural glycobiology

Although NMR spectroscopy has great potential to provide us with detailed structural information on oligosaccharides and glycoconjugates, the carbohydrate NMR analyses have been hampered by the severe spectral overlapping and the insufficiency of the conformational restraints. Recently, ultra-high field NMR spectrometers have become available for applications to structural analyses of biological macromolecules. Here we demonstrate that ultra-high fields offer not only increases in sensitivity and chemical shift dispersion but also potential benefits for providing unique information on chemical exchange and relaxation, by displaying NMR spectral data of oligosaccharide, glycoprotein, and glycolipid systems recorded at a 21.6 T magnetic field (corresponding to 920 MHz (1)H observation frequency). The ultra-high field NMR spectroscopy combined with sugar library and stable-isotope labeling approaches will open new horizons in structural glycobiology.     

Just a spoonful of sugar: Short glycans affect protein properties and functions

Glycosylation has a strong impact on the chemical and physical properties of proteins and on their activity. The heterogeneous nature of this modification complicates the elucidation of the role of each glycan, thus slowing down the progress in glycobiology. Nevertheless, the great advances recently made in protein engineering and in the chemical synthesis, and semisynthesis of glycoproteins are giving impulse to the field, fostering important discoveries. In this review, we report on the findings of the last two decades on the importance that the attachment site, linkage, and composition of short glycans have in affecting protein properties and functions.