Vol.5 No.3 2012

66/94

Research paper−201−Synthesiology - English edition Vol.5 No.3 pp.201-215 (Dec. 2012) and they become functionally-matured molecules after receiving proper glycan attachments (glycosylation). A group of glycoproteins consist of uniform protein moiety, but their glycan moieties are quite inhomogeneous. For example, immunoglobulin G (IgG) has double stranded, simple N-linked glycans (N-glycans), which have a wide variety of structures (36 types). However, it is very difficult to purify glycoproteins consisting of homogenous glycan structures. Moreover, it is almost impossible to synthesize glycoproteins consisting of homogenous glycan structures. For these reasons, the variety of glycan functions attributed to slight alteration of glycan structures is so far hardly analyzed.Glycans binding to glycoproteins are roughly classified into N-glycans and O-linked glycans (O-glycans). N-glycans are attached to the asparagine-X-threonine or -serine (Asn-X-Thr/Ser) sequence, and this preference is relatively conserved among species. In contrast, O-glycans can be attached to any part of threonine or serine. In humans, there are about 20 members of ppGalNac-T, a glycotransferase family which initiates synthesis of O-glycans, and each of them exhibits various expression patterns along with differentiation or canceration of cells. This means binding sites of O-glycans are affected by differentiation or canceration of cells. Unfortunately, no technology to identify the binding site of O-glycan has been developed yet. It is a natural habit of scientists to think that there should 1 IntroductionGlycans are often regarded as the third biological chains of fundamental biopolymers, following nucleic acids (first chain) and proteins (second chain). Proteins are easily understandable as they are the principal gene products (nucleic acids). The protein synthetic mechanism is similar among species, and thus the principles clarified in lower organisms are also applicable to humans. In contrast, glycans are synthesized sequentially by more than 180 kinds of enzymes called glycosyltransferases.The substrate specificity of glycans amazingly changes along with the evolution of species, resulting in wide differences in monosaccharides which make up glycans and also in their structural sequences between the lower organisms and humans. This is interesting, as nucleotides and amino acids which make up nucleic acids and proteins have barely evolved. There are a few monosaccharides that are common between bacteria and humans, but the majority varies. Equally, with animals and plants, a large part of the monosaccharides are uncommon. Glycans also differ between anthropoids including humans and other mammals such as pigs, cattle and lower species. In general, glycans are attached to proteins and phosphates forming glycoproteins and glycolipids, respectively. Most of the membrane proteins and serum proteins are glycoproteins, - A 10-year strategy of the Research Center for Medical Glycoscience of AIST-We proposed a 10-year strategy for the development of a new scientific field, glycoscience. Initially, we developed basic technological tools to help scientists and engineers entering this field. As the first project, we exhaustively discovered glycogenes and carried out their functional analyses. The fruits of this work led to several follow-on projects: (1) technology for enzyme synthesis of glycans, (2) technology for structural analysis of glycans, and (3) analysis of biological functions of glycans. The basic tools, developed in the first 5 years of our 10-year strategy, were applied to the development of more useful products, e.g., disease biomarkers, particularly for cancer diagnosis. We are also close to achieving the practical use of a liver fibrosis marker and a cholangiocarcinoma marker for diagnosis. Moreover, we are pursuing development of biomarkers for diagnosis of other cancers. The successful research results for these 10 years have now been transferred to the world, in particular, Asian countries, and yielded collaborative research contracts with domestic and overseas research groups.Development of basic tools for glycoscience and their application to cancer diagnosisKeywords : Glycan, N-glycan, O-glycan, glycosyltransferase, glycogene, lectin, lectin array, mass-spectrometry, IGOT, biomarker, liver fibrosis, liver cancer, cholangiocarcinoma[Translation from Synthesiology, Vol.5, No.3, p.190-203 (2012)]Hisashi Narimatsu Research Center for Medical Glycoscience (RCMG), AIST Tsukuba Central 2, 1-1-1 Umezono, Tsukuba 305-8568, Japan E-mail : Original manuscript received March 5, 2012, Revisions received April 13, 2012, Accepted April 25, 2012

※このページを正しく表示するにはFlashPlayer9以上が必要です