Construction and Structural Characterization of Versatile Lactosaminoglycan-Related Compound Library for the Synthesis of Complex Glycopeptides and Glycosphingolipids
| ISSN: | 1522-2667 0931-7597 |
|---|---|
| DOI: | 10.1002/chin.200714203 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4d1ab01ff2dee03dddc6f8395f23441 https://doi.org/10.1002/chin.200714203 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....a4d1ab01ff2dee03dddc6f8395f23441 |
| Autor: | Naoki Fujitani, Takahiko Matsushita, Kentarou Naruchi, Shin-Ichiro Nishimura, Hirosato Kondo, Tomoki Hamamoto, Hiroshi Hinou, Masaki Kurogochi, Hiroki Shimizu |
| Rok vydání: | 2007 |
| Předmět: |
Free Radicals
Stereochemistry Molecular Sequence Data Combined use Disaccharide Stereoisomerism Chemical synthesis Lactosaminoglycan Glycosphingolipids chemistry.chemical_compound Polysaccharides Glycosyltransferase Carbohydrate Conformation Combinatorial Chemistry Techniques chemistry.chemical_classification biology Organic Chemistry Glycopeptides Amino Sugars General Medicine Oligosaccharide Glycosyltransferase activity Glycopeptide Amino acid Carbohydrate Sequence Aminosugar chemistry biology.protein Substrate specificity Carbohydrate conformation |
| Zdroj: | ChemInform. 38 |
| ISSN: | 1522-2667 0931-7597 |
| DOI: | 10.1002/chin.200714203 |
| Popis: | We have established a facile and efficient protocol for the preparative-scale synthesis of various compound libraries related to lactosaminoglycans: cell surface oligosaccharides composed of N-acetyllactosamine as a repeating disaccharide unit, based on chemical and enzymatic approaches. Substrate specificity and feasibility of a bacterial glycosyltransferase, Neisseria meningitidis beta1,3-N-acetylglucosaminyltransferase (LgtA), were investigated in order to synthesize various key intermediates suited for the construction of mammalian O-glycopeptides and glycosphingolipids containing poly-N-acetyllactosamine structures. Recombinant LgtA exhibited the highest glycosyltransferase activity with strongly basic conditions (pH = 10, glycine-NaOH buffer) and a broad range of optimal temperatures from 20 to 30 degrees C. Interestingly, it was found that LgtA discriminates L-serine and L-threonine and functions both as a core-1 beta1,3-N-acetylglucosaminyltransferase and core-2 beta1,3-N-acetylglucosaminyltransferase toward Fmoc-Ser derivatives, while LgtA showed only core-2 beta1,3-N-acetylglucosaminyltransferase activity in the presence of Fmoc-Thr derivatives. Combined use of LgtA with human beta1,4-galactosyltransferase allowed for controlled sugar extension reactions from synthetic sugar amino acids and gave synthetic lactosaminoglycans, such as a decasaccharide derivative, Galbeta(1 --> 4)GlcNAcbeta(1 --> 3)Galbeta(1 --> 4)GlcNAcbeta(1 --> 3)Galbeta(1 --> 4)GlcNAcbeta(1 --> 3)Galbeta(1 --> 4)GlcNAcbeta(1 --> 6)[Galbeta(1 --> 3)]GalNAcalpha1 --> Fmoc-Ser-OH (6), and a dodecasaccharide derivative, Galbeta(1 --> 4)GlcNAcbeta(1 --> 3)Galbeta(1 --> 4)GlcNAcbeta(1 --> 3)Galbeta(1 --> 4)GlcNAcbeta(1 --> 6)[Galbeta(1 --> 4)GlcNAcbeta(1 --> 3)Galbeta(1 --> 4)GlcNAcbeta(1 --> 3)Galbeta(1 --> 3)]GalNAcalpha1 --> Fmoc-Ser-OH (9). A partially protected pentasaccharide intermediate, GlcNAcbeta(1 --> 3)Galbeta(1 --> 4)GlcNAcbeta(1 --> 6)[Galbeta(1 --> 3)]GalNAcalpha1 --> Fmoc-Thr-OH (11), was applied for the microwave-assisted solid-phase synthesis of a MUC1-related glycopeptide 19 (MW = 2610.1). The findings suggest that this sugar extension strategy can be employed for the modification of lactosyl ceramide mimetic polymers to afford convenient precursors for the synthesis of various glycosphingolipids. |
| Databáze: | OpenAIRE |
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