| 1. |
- Sardzik, Robert, et al.
(författare)
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Chemoenzymatic Synthesis of O-Mannosylpeptides in Solution and on Solid Phase
- 2012
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 134:10, s. 4521-4524
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Tidskriftsartikel (refereegranskat)abstract
- O-Mannosyl glycans are known to play an important role in regulating the function of alpha-dystroglycan (alpha-DG), as defective glycosylation is associated with various phenotypes of congenital muscular dystrophy. Despite the well-established biological significance of these glycans, questions regarding their precise molecular function remain unanswered. Further biological investigation will require synthetic methods for the generation of pure samples of homogeneous glycopeptides with diverse sequences. Here we describe the first total syntheses of glycopeptides containing the tetrasaccharide NeuNAc alpha 2-3Gal beta 1-4GlcNAc beta 1-2Man alpha, which is reported to be the most abundant O-mannosyl glycan on alpha-DG. Our approach is based on biomimetic stepwise assembly from the reducing end and also gives access to the naturally occurring mono-, di-, and trisaccharide substructures. In addition to the total synthesis, we have developed a one-pot enzymatic cascade leading to the rapid synthesis of the target tetrasaccharide. Finally, solid-phase synthesis of the desired glycopeptides directly on a gold microarray platform is described.
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| 2. |
- Shi, Jin-Min, et al.
(författare)
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Substrate promiscuities of a bacterial galactokinase and a glucose-1-phosphate uridyltransferase enable xylose salvaging
- 2022
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Ingår i: Green Chemistry. - : Royal Society of Chemistry (RSC). - 1463-9262 .- 1463-9270. ; 24:9, s. 3717-3722
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Tidskriftsartikel (refereegranskat)abstract
- Galactokinases (GalKs) are structurally conserved proteins that exist in all domains of life. These enzymes catalyse the transfer of a phosphate group from adenosine triphosphate (ATP) to the anomeric hydroxyl group of galactose and show only negligible substrate promiscuities toward other sugars such as glucose, mannose, or xylose. Here we describe a peculiar GalK orthologue from the bacterium Solitalea canadensis (ScGalK) with relaxed acceptor sugar requirements, which also converts xylose to xylose-1-phosphate in the presence of ATP. Investigating the surrounding genomic DNA region of the ScGalK gene revealed a putative Glucose-1-phosphate Uridyltransferase (ScGPUT) candidate in close proximity, and the recombinant gene product of ScGPUT was able to convert xylose-1-phosphate into uridine diphosphate xylose (UDP-xylose) in the presence of uridine triphosphate (UTP). Given that UDP-xylose is an essential building block for the generation of xylose-containing glycoconjugates in bacteria, converting xylose using these two enzymes into UDP-xylose significantly reduces the cofactor requirements compared to the known standard xylose regeneration via the pentose phosphate pathway.
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