<i>C</i>‐Glycosidic UDP‐GlcNAc Analogues as Inhibitors of UDP‐GlcNAc 2‐Epimerase

Stolz, Florian; Blume, Astrid; Hinderlich, Stephan; Reutter, Werner; Schmidt, Richard R.

doi:10.1002/ejoc.200400197

Cited by 25 publications

(17 citation statements)

References 30 publications

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“…The 2-Ophosphoryl group present in compounds 14 and 16 may be regarded as mimic of the diphosphate bridge in the nucleotide sugar and-although lacking the charged moiety of the glycosyl phosphate-could provide a proper formal distance to fit into the binding site of the glycosyl transferase, an important aspect to maintain binding potency of synthetic inhibitors. 19 In addition to the analogues of D D-glycero-D D-manno-heptose, C-glycosides of the L L-glycero-D D-manno-configuration were prepared in a similar fashion. Thus, condensation of 17 20 with pentane-2,4-dione proceeded in good yield to afford a complex mixture containing the anomeric 2-oxo-propyl heptopyranosides 18 and 20.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis of C-glycosides related to glycero-β-d-manno-heptoses

Graziani

Amer

Zamyatina

et al. 2005

Tetrahedron: Asymmetry

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Section: Resultsmentioning

confidence: 99%

“…, 3 J C,P = 2.7 Hz, C-1),19.85, 19.75, 19.68, 19.57,19.56 (5C, CH3 , Ac), 8.26 (CH 3 , Et 3 N); 31 P NMR (MeOD): d 0.9; TOF-ES-MS: m/z = 543.118 [M+H] + . Calcd 543.147 [M+H] + .…”

mentioning

confidence: 99%

Synthesis of C-glycosides related to glycero-β-d-manno-heptoses

Graziani

Amer

Zamyatina

et al. 2005

Tetrahedron: Asymmetry

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“…In the light of our new results, it is not surprising that synthetic derivatives of UDP (41,42) have been found to effectively inhibit the enzyme. According to our studies, another apparent requirement for a potent inhibitor is the presence of two or three negative charges.…”

Section: Fig 5 Model For the Design Of Udp-glcnac 2-epimerase Inhibmentioning

confidence: 99%

Characterization of Ligand Binding to the Bifunctional Key Enzyme in the Sialic Acid Biosynthesis by NMR

Blume

Benie

Stolz

et al. 2004

Journal of Biological Chemistry

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The bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase is the key enzyme for the biosynthesis of sialic acids. As terminal components of glycoconjugates, sialic acids are associated with a variety of pathological processes such as inflammation and cancer. For the first time, this study reveals characteristics of the interaction of the epimerase site of the enzyme with its natural substrate, UDP-N-acetylglucosamine (UDP-GlcNAc) and derivatives thereof at atomic resolution. Saturation transfer difference NMR experiments were crucial in obtaining ligand binding epitopes and to rank ligands according to their binding affinities. Employing a fragment based approach, it was possible to assign the major component of substrate recognition to the UDP moiety. In particular, the binding epitopes of the uridine moieties of UMP, UDP, UDP-GalNAc, and UDP-GlcNAc are rather similar, suggesting that the binding mode of the UDP moiety is the same in all cases. In contrast, the hexopyranose units of UDP-GlcNAc and UDP-GalNAc display small differences reflecting the inability of the enzyme to process UDP-GalNAc. Surprisingly, saturation transfer difference NMR titrations show that UDP has the largest binding affinity to the epimerase site and that at least one phosphate group is required for binding. Consequently, this study provides important new data for rational drug design.

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“…156 Through a similar protocol, azido glucose 648 (derived from N-acetylglucosamine) was transformed via the imidate to azido Compounds such as 647 or 651 are applied as building elements in the synthesis of different carbopeptoid oligomers. 156,157 Azido amino sugars in the form of orthogonally protected sugar diamino acids were synthetized from acetylated sugar β-amino nitrile derivative 652. Deacetalization of 652, with subsequent exchange of the more reactive hydroxy group at C-6 to azide, resulted in azido nitrile 654, the methoxymethyl etherification of which, followed by nitrile hydrolysis, yielded azido amino acid 656 (Scheme 132).…”

Section: Amentioning

confidence: 99%

Synthesis of Carbocyclic and Heterocyclic β-Aminocarboxylic Acids

2013

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Introduction 1116 2. Carbocyclic β-Amino Acids 1118 2.1. Syntheses of Five-or Six-Membered Carbocyclic β-Amino Acids 1118 2.1.1. Carbocyclic β-Amino Acids from β-Keto Esters 1119 2.1.2. Carbocyclic β-Amino Acids by Metathesis 1119 2.1.3. Carbocyclic β-Amino Acids by Amino Group Conjugate Addition 1122 2.1.4. Carbocyclic β-Amino Acids by Cycloaddition 1124 2.1.5. Carbocyclic β-Amino Acids by Desymmetrization of meso-Anhydrides 1124 2.1.6. Carbocyclic β-Amino Acids from Natural Sources 1125 2.1.7. Miscellaneous 1127 2.2. Syntheses of Small-Ring Carbocyclic β-Amino Acids 1128 2.3. Syntheses of Carbocyclic β-Amino Acids with Larger Ring Systems 1129 2.4. Synthesis of Functionalized Carbocyclic β-Amino Acids 1131 2.4.1. Syntheses of Functionalized Cyclic β-Amino Acids by C−C Double Bond Functionalization 1131 2.4.2. Several Relevant Routes to Functionalized Cyclic β-Amino Acids Other Than Functionalization of the Ring C−C Double Bond 1137 3. Cyclic β-Amino Acids with a Heteroatom in the Ring 1137 3.1. Syntheses of Cyclic β-Amino Acids with a N Atom in the Ring 1138 3.1.1. Three-and Four-Membered N-Containing Cyclic β-Amino Acids 1138 3.1.2. Five-Membered N-Containing Cyclic β-Amino Acids 1138 3.1.3. Six-Membered N-Containing Cyclic β-Amino Acids 1145 3.1.4. N-Containing Cyclic β-Amino Acids with Larger Ring Systems 1148 3.2. Syntheses of Cyclic β-Amino Acids with an O Atom in the Ring 1148 3.2.1. Four-Membered O-Containing Cyclic β-Amino Acids 1148 3.2.2. Five-Membered O-Containing Cyclic β-Amino Acids 1149 3.2.3. Six-Membered O-Containing Cyclic β-Amino Acids 1155 3.3. Cyclic β-Amino Acids with Other Heteroatoms in the Ring 1159 4. Some Relevant Biological Properties of Cyclic β-Amino Acids 1160 4.1. Cyclic β-Amino Acids Possessing Antifungal or Antibacterial Properties 1160 4.2. Antiviral Cyclic β-Amino Acids 1162 4.3. Cyclic β-Amino Acids with Antitumoral Properties 1162 4.4. Cyclic β-Amino Acids with Cardioprotective

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C‐Glycosidic UDP‐GlcNAc Analogues as Inhibitors of UDP‐GlcNAc 2‐Epimerase

Cited by 25 publications

References 30 publications

Synthesis of C-glycosides related to glycero-β-d-manno-heptoses

Synthesis of C-glycosides related to glycero-β-d-manno-heptoses

Characterization of Ligand Binding to the Bifunctional Key Enzyme in the Sialic Acid Biosynthesis by NMR

Synthesis of Carbocyclic and Heterocyclic β-Aminocarboxylic Acids

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