ライフサイエンスコーパス: ManNAc

1 ManNAc administration yielded survival beyond P3 in 43%

2 ManNAc treatment appeared to ameliorate the hyposialylat

3 1,3,4-O-acetylated N-acetylmannosamine (Ac(3)ManNAc) to deliver ManNAc-6-phosphate (ManNAc-6-P), a cr

4 were developed to provide a library of Ac(3)ManNAc-6-phosphoramidates that were evaluated in a serie

5 ay between HDACi activity (held by both Bu(4)ManNAc and Bu(5)Man) and NF-kappaB activity, which was s

6 d in cell mobility and demonstrate that Bu(4)ManNAc breaks the confounding link between beneficial HD

7 The active compound Bu(4)ManNAc reduced both MUC1 expression and MMP-9 activity (

8 er-butanoylated N-acetyl-D-mannosamine (Bu(4)ManNAc), a SCFA-hexosamine cancer drug candidate with ac

9 which was selectively down-regulated by Bu(4)ManNAc.

10 poteichoic acids (LTAs) with poly-(beta1->4)-ManNAc backbones substituted with phosphoethanolamine.

11 We synthesized a novel inhibitor, 6-O-acetyl-ManNAc, which is more potent than those previously teste

12 s revealed by 1H NMR had 60-70% O-acetylated ManNAc residues that contained acetyl groups at O-3, wit

13 ressed by the addition of tetra-O-acetylated ManNAc, which is easily taken up by the cells.

14 tamidoglucal and [N-(14)C]acetylmannosamine (ManNAc) from UDP-[(14)C]GlcNAc.

15 th exogenously supplied N-acetylmannosamine (ManNAc) analogs has many potential biomedical and biotec

16 he high affinity ligand N-acetylmannosamine (ManNAc) binds in the S1 site, predominantly via the acet

17 sformation of unnatural N-acetylmannosamine (ManNAc) derivatives.

18 AS) in combination with N-acetylmannosamine (ManNAc) feeding has been shown to overcome this limitati

19 -N-acetylglucosamine to N-acetylmannosamine (ManNAc) followed by its phosphorylation to ManNAc 6-phos

20 dvanced to a variety of N-acetylmannosamine (ManNAc) frameworks, using an intramolecular O-->N acetyl

21 N-Acetylmannosamine (ManNAc) is the first committed intermediate in the siali

22 glucosamine 2-epimerase/N-acetylmannosamine (ManNAc) kinase (GNE/MNK), result in hereditary inclusion

23 e sialic acid precursor N-acetylmannosamine (ManNAc) led to improved sialylation and survival of muta

24 acetylated at O3 of the N-acetylmannosamine (ManNAc) residue.

25 y TagA, which transfers N-acetylmannosamine (ManNAc) to the C4 hydroxyl of a membrane-anchored N-acet

26 the production of free N-acetylmannosamine (ManNAc), has not been defined.

27 sed on fucose (Fuc) and N-acetylmannosamine (ManNAc), were incorporated into fucosylated and sialylat

28 cetamido-2,3-dideoxy-beta-d-mannuronic acid (ManNAc(3NAc)A), is thought to be produced by five enzyme

29 of the three HexNAc residues are GlcNAc and ManNAc and the third can be either GlcNAc or GalNAc.

30 -chains in biologically important GlcNAc and ManNAc monosaccharides and in a betaGlcNAc-(1->4)-betaGl

31 2-C1' torsion angle (theta(1)) in GlcNAc and ManNAc residues.

32 nformations of the C2-N2 bonds of GlcNAc and ManNAc.

33 e JGS4143 LTA also had a terminal ribose and ManNAc instead of ManN in the core region, suggesting th

34 he P. aeruginosa PAO1 (O5) B-band O-antigen, ManNAc(3NAc)A, has been shown to be critical for virulen

35 ventions targeting these mechanisms, such as ManNAc supplementation, may provide novel means to break

36 sisting of a -->6)-alpha-GalNAc-(1-->4)-beta-ManNAc-(1-->4)-beta-GlcNAc-(1--> trisaccharide that is s

37 backbone of -->6)-alpha-GlcNAc-(1-->4)-beta-ManNAc-(1-->4)-beta-GlcNAc-(1-->, in which the alpha-Glc

38 (SCWP) with the repeat structure [-->4)-beta-ManNAc-(1-->4)-beta-GlcNAc-(1-->6)-alpha-GlcNAc-(1-->]n,

39 in the 2 (17%) or 3 (25%) position and beta-ManNAc residues may be O-acetylated in the 4 (6%) or 6 (

40 phosphorylation of the N-acylmannosamines by ManNAc 6-kinase in the first step of the pathway.

41 by phosphodiester linkages [ --> 6)-alpha-D-ManNAc-(1 --> OPO3 (-)-->]n.

42 nds contain an alpha-d-GlcNAc-(1-->4)-beta-d-ManNAc-(1-->4)-beta-d-GlcNAc backbone that is modified b

43 N-acetylmannosamine (Ac(3)ManNAc) to deliver ManNAc-6-phosphate (ManNAc-6-P), a critical intermediate

44 Roles for UDP-GlcNAc 2-epimerase/ManNAc 6-kinase (GNE) beyond controlling flux into the s

45 The genes for UDP-GlcNAc-2-epimerase/ManNAc kinase (EK), sialic acid 9-phosphate synthase (SA

46 UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) catalyzes the first two committed st

47 GNE (UDP-GlcNAc 2-epimerase/ManNAc kinase) myopathy is a rare muscle disorder associ

48 expression of SAS and UDP-GlcNAc 2-epimerase/ManNAc kinase, the bifunctional enzyme initiating sialic

49 kinase domain of the UDP-GlcNAc-2-epimerase/ManNAc kinase.

50 e bifunctional enzyme UDP-GlcNAc-2-epimerase/ManNAc kinase.

51 ic acid biosynthesis, UDP-GlcNAc 2-epimerase/ManNAc kinase.

52 y a Gne cDNA encoding UDP-GlcNAc 2-epimerase:ManNAc kinase rescued PSA synthesis.

53 ue for Neu5Ac and highest kcat/Km values for ManNAc and pyruvate, which makes CgNal favor Neu5Ac synt

54 acetylglucosamine 2-epimerase that generates ManNAc directly from the dinucleotide-sugar precursor de

55 merase are two enzymes capable of generating ManNAc from UDP-GlcNAc and GlcNAc, respectively.

56 ilization of the three amino sugars, GlcNAc, ManNAc, and sialic acid.

57 sphate acceptor and is inactive with GlcNAc, ManNAc, glucose, galactose, mannose, GalN, and GlcN.

58 at CP5 synthesis does not involve the GlcNAc-ManNAc linkage unit of WTA and may instead utilize anoth

59 chitecture in ManNAc-treated mice highlights ManNAc as a potential treatment for humans affected with

60 eoxy-3-O-methyl-D-mannose inhibits the human ManNAc kinase domain of the UDP-GlcNAc-2-epimerase/ManNA

61 al restoration of glomerular architecture in ManNAc-treated mice highlights ManNAc as a potential tre

62 s, the mechanisms that control intracellular ManNAc levels are important regulators of sialic acid pr

63 Ac is replaced by the higher affinity ligand ManNAc.

64 mopolymer of O-acetylated, alpha1-->6-linked ManNAc 1-phosphate that is distinct from the capsule str

65 id (GlcNAc-pp-undecaprenyl, lipid I) to make ManNAc-beta-(1,4)-GlcNAc-pp-undecaprenyl (lipid II).

66 ate and 2-acetamido-2-deoxy-d-mannopyranose (ManNAc) to 3FNeu5Ac, but stereocontrol of the fluorine i

67 Glc), galactose (Gal), N-acetyl mannosamine (ManNAc), and N-acetylglucosamine (GlcNAc).

68 The N-acetyl-D-mannosamine (ManNAc) analog Ac5ManNTGc, a non-natural metabolic precu

69 alian cells utilizes N-acetyl-D-mannosamine (ManNAc) as a natural metabolic precursor and has the rem

70 ialic acid precursor N-acetyl-D-mannosamine (ManNAc) to NPHS2-Angptl4 transgenic rats it increased th

71 c) from pyruvate and N-acetyl-D-mannosamine (ManNAc).

72 ialic acid precursor N-acetyl-D-mannosamine (ManNAc).

73 Furthermore, in HFD-fed mice, ManNAc normalized IgG sialylation and prevented obesity-

74 resolution, MNK.ManNAc.ADP (1.82 A) and MNK.ManNAc 6-phosphate . ADP (2.10 A).

75 plexes with ManNAc at 1.64 A resolution, MNK.ManNAc.ADP (1.82 A) and MNK.ManNAc 6-phosphate . ADP (2.

76 ses engendered by regioisomerically modified ManNAc, GlcNAc, and GalNAc analogues in MDA-MB-231 cells

77 olase or lyase), nanK (ManNAc kinase), nanE (ManNAc-6-P 2-epimerase), neuS (polysialyltransferase) an

78 s in nanA (sialate aldolase or lyase), nanK (ManNAc kinase), nanE (ManNAc-6-P 2-epimerase), neuS (pol

79 lity to biosynthetically process non-natural ManNAc analogs.

80 The combined results indicate that neither ManNAc-6-P nor specific or non-specific phosphatase are

81 rs, and to efficiently elongate the dimer of ManNAc-1-phosphate.

82 The results also support evaluation of ManNAc as a treatment not only for HIBM but also for ren

83 sect cells and was overcome by expression of ManNAc kinase.

84 an epimerase that catalyzes the formation of ManNAc from UDP-GlcNAc via a 2-acetamidoglucal intermedi

85 Identification of ManNAc 6-kinase as a bottleneck for unnatural sialic aci

86 A panel of ManNAc analogs bearing various modifications on the hydr

87 tion of GlcNAc kinase for phosphorylation of ManNAc in insect cells and was overcome by expression of

88 ions in the transport and phosphorylation of ManNAc.

89 utations in GNE that limit the production of ManNAc-6-P.

90 l intermediate and the extremely low rate of ManNAc formation likely were a result of the in vitro as

91 ral alterations of the N-acyl substituent of ManNAc.

92 Here we show that ManNAc-6-phosphate (ManNAc-6-P) is not an obligate sialate precursor in Esch

93 (Ac(3)ManNAc) to deliver ManNAc-6-phosphate (ManNAc-6-P), a critical intermediate in sialic acid bios

94 ntermediate N-acetylmannosamine-6-phosphate (ManNAc-6P) relieves NanR promoter binding.

95 UDP-N-acetyl-D-glucosamine-2-epimerase, poly-ManNAc-1-phosphate-transferase, and O-acetyltransferase,

96 ine-2-epimerase and CsaB the functional poly-ManNAc-1-phosphate-transferase.

97 (G1) binding sites, the terminal pyruvylated ManNAc moiety serves as the nearly exclusive SCWP anchor

98 tase are necessary to generate the requisite ManNAc for sialate biosynthesis.

99 active K66A mutant in complex with substrate ManNAc-6P.

100 erties, while also being more effective than ManNAc at increasing sialic acid levels in GNE-deficient

101 etabolism in apoptosis by demonstrating that ManNAc analogs can modulate apoptosis both indirectly vi

102 Here we show that ManNAc-6-phosphate (ManNAc-6-P) is not an obligate siala

103 Direct biochemical analysis showed that ManNAc-6-P was stable in a nanE mutant extract.

104 When plasmid pXO2 was absent, the ManNAc/Gal ratio decreased, while the Glc/Gal ratio incr

105 However, although the ManNAc residues in JGS4143 LTA were phosphoethanolamine-

106 The binding of the ManNAc pyranose ring differs markedly between the two in

107 (ManNAc) followed by its phosphorylation to ManNAc 6-phosphate and has a direct impact on the sialyl

108 Subsequently, CsaB was shown to transfer ManNAc-1P onto O-6 of the non-reducing end sugar of prim

109 mannosaminuronic acid (UDP-ManNAcA) by a UDP-ManNAc dehydrogenase encoded by S. aureus cap5O.

110 s epimerized to UDP-N-acetylmannosamine (UDP-ManNAc) and then oxidized to UDP-ManNAcA.

111 (UDP-GlcNAc) to UDP-N-acetylmannosamine (UDP-ManNAc).

112 y function as UDP-GlcNAc 2-epimerase and UDP-ManNAc dehydrogenase enzymes, respectively, in the synth

113 reversible conversion of UDP-GlcNAc and UDP-ManNAc.

114 bpI can be combined in vitro to generate UDP-ManNAc(3NAc)A in a single reaction vessel, thereby provi

115 ubating Cap5P and UDP-GlcNAc (to produce UDP-ManNAc), together with Cap5O, NAD(+), and a reducing age

116 In this study, we show that UDP-ManNAc is oxidized to UDP-N-acetylmannosaminuronic acid

117 The UDP-ManNAc dehydrogenase activity of purified Cap5O was asse

118 erted approximately 10% of UDP-GlcNAc to UDP-ManNAc as detected by gas chromatography-mass spectromet

119 The epimerization of UDP-GlcNAc to UDP-ManNAc occurred over a wide pH range and was unaffected

120 y-state ordered Bi-Bi mechanism in which UDP-ManNAc binds first and UDP is released last.

121 and 2.5 times higher than that achieved with ManNAc feeding.

122 e found to be lower than those achieved with ManNAc supplementation due to feedback inhibition of the

123 vel 7.5 times higher than that achieved with ManNAc supplementation, creating a bottleneck in the con

124 N-acetylmannosamine kinase in complexes with ManNAc at 1.64 A resolution, MNK.ManNAc.ADP (1.82 A) and

125 The lower Neu5Ac levels obtained with ManNAc feeding suggested limitations in the transport an

126 s of Neu5Ac compared to levels obtained with ManNAc feeding with SAS expression alone.