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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

54 Ac is replaced by the higher affinity ligand ManNAc.

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

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

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

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

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

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

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

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

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

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

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

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

67 lity to biosynthetically process non-natural ManNAc analogs.

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

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

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

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

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

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

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

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

76 ions in the transport and phosphorylation of ManNAc.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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