ライフサイエンスコーパス: polyglutamate

1 H]compound 1 was metabolized to (3)H-labeled polyglutamates.

2 yglutamyl tail from folyl and p-aminobenzoyl polyglutamates.

3 TX accumulation and metabolism to long-chain polyglutamates.

4 rotate, was rapidly converted to long-chain polyglutamates.

5 the gamma-linked glutamates from folic acid polyglutamates.

6 d penultimate gamma-linkages of methotrexate polyglutamates.

7 rom HL-60 cells were similar on methotrexate polyglutamates.

8 Polyglutamate, a peptide reported to mitigate aluminum t

9 ding of glycine and 5-formyltetrahydrofolate polyglutamate, a slow tight-binding inhibitor.

10 metabolically trapped in mammalian cells as polyglutamates, a process catalyzed by folylpoly-gamma-g

11 i) folates continuously enter the vacuole as polyglutamates, accumulate there, are hydrolyzed by GGH,

12 Whereas C1 and C2 polyglutamates accumulated to similar levels in WT and R

13 basis for differences between long chain MTX polyglutamate accumulation between different leukemia ce

14 We now report that LY231514 and its polyglutamates also markedly inhibit other key folate-re

15 t study, we measured intracellular levels of polyglutamated anabolites of 1031U89, 1843U89, and three

16 Each TS inhibitor was anabolized to polyglutamated analogues with one to five added glutamyl

17 ound is as potent an enzyme inhibitor as its polyglutamated analogues.

18 Polyanions such as polyglutamate and double-stranded and single-stranded DN

19 resembles the Raman amide I band of ionized polyglutamate and polylysine, peptides which adopt a pol

20 ication were 1.6 and 5 nmol/L for individual polyglutamates and 1.5 and 4.5 nmol/L for total polyglut

21 was contributed by 5-methyltetrahydrofolate polyglutamates and 5,10-methenyltetrahydrofolate polyglu

22 s caused extensive deglutamylation of folate polyglutamates and lowered the total folate content by a

23 ts transport characteristics with respect to polyglutamates and reduced folates are not identical to

24 en leukemia cells that accumulate long chain polyglutamates and those that do not were differences in

25 y this route was rapidly converted to higher polyglutamates and, when grown with 25 nM 5-formyl-tetra

26 selectivity of the transporter for MTX, MTX polyglutamates, and physiological folates.

27 selectivity of this transporter for MTX, MTX polyglutamates, and physiological folates.

28 itochondrial FPGS is required because folate polyglutamates are not substrates for transport across t

29 lpolyglutamates in vacuoles implies that the polyglutamates are somehow protected from GGH attack.

30 to SHMT, showing that anions compete for the polyglutamate binding site.

31 Both polyaspartate and polyglutamate blocked LPL and chylomicron binding to GPI

32 showed approximately 85% reduction in folate polyglutamates, but cells expressing LeGGH3 did not, con

33 the biosynthesis of F(420)-0 (F(420) without polyglutamate), by transferring the lactyl phosphate moi

34 DNA-like polyanion chains (e.g. heparin and polyglutamate) can mediate the transfer.

35 retention (associated with tissue storage of polyglutamates) can contribute to clinical toxicities, 1

36 rmidis contains the cap operon, encoding the polyglutamate capsule, a major virulence factor in Bacil

37 lthough transport gradually decreased as the polyglutamate chain length increased, both MTX-Glu(2) an

38 cid concentrations, and 4) increased average polyglutamate chain lengths of folate cofactors.

39 The polyglutamate chain, which does not contribute to cataly

40 HDMTX plus MP yielded 2-fold higher MTX polyglutamate concentrations than LDMTX plus MP (2148 +/

41 for neuronal survival through hydrolysis of polyglutamate-containing substrates.

42 by a 2-fold increase in accumulation of MTX polyglutamate derivatives and a approximately 50% decrea

43 ct to steady state kinetics, chain length of polyglutamate derivatives formed, and end-product inhibi

44 The excess folate accumulated as polyglutamate derivatives in the vacuole.

45 enous folate pools were modestly reduced but polyglutamate derivatives of DDATHF and ALIMTA (LY231514

46 oform was also capable of forming long chain polyglutamate derivatives of the model folate, 5,10-dide

47 The biosynthetic pathway converts GTP to polyglutamated derivatives of tetrahydrofolate (THF), es

48 of thioguanine nucleotides and methotrexate polyglutamates did not differ between the 4 BMI groups (

49 , there was no detectable transfer of folate polyglutamates either from the cytosol to mitochondria,

50 l glutamates to folate, forming gamma-linked polyglutamate folates of varying lengths.

51 these parasites could still convert pABA to polyglutamated folates, albeit at a very low level, but

52 al pteroylmonoglutamate was converted to the polyglutamate form, most of the body folate was visceral

53 ndogenously, folates exist in the brain in a polyglutamated form with 1-7 terminal glutamates (approx

54 talyze sequential reactions in coenzyme F420 polyglutamate formation: a gamma-glutamyl ligase adds 1-

55 ubstrate are tight-binding ligands, and that polyglutamate forms enhance the affinity of both substra

56 Metabolism to more biologically active polyglutamate forms is also potentiated for MTX and othe

57 ethod does not distinguish between mono- and polyglutamate forms of the coenzyme.

58 w Kms for folylpolyglutamate synthetase, and polyglutamate forms of these inhibitors are accumulated

59 yltetrahydrofolate (5-CHO-H4PteGlun) and its polyglutamate forms to rabbit liver cytosolic serine hyd

60 lished that LY231514 and its synthetic gamma-polyglutamates (glu3 and glu5) exert potent inhibition a

61 the presence of formylated tetrahydrofolate polyglutamates in addition to methylated derivatives in

62 method for the determination of methotrexate polyglutamates in dried blood spots (DBS).

63 n mechanism of self-assembly for star-shaped polyglutamates in nonsalty aqueous solutions is identifi

64 onomers, and to contain tightly bound folate polyglutamates in vivo.

65 mylation, augmented hydrolysis of antifolate polyglutamates, increased expression and mutation of tar

66 f these nanosized soft-assembled star-shaped polyglutamates is also described, enabling the translati

67 rates and a marked preference for long-chain polyglutamates (Km values for glu4 versus glu1 derivativ

68 similarities were present in the folyl-gamma-polyglutamate ligases.

69 several key folate-requiring enzymes via its polyglutamated metabolites.

70 sting cofactor 5,10-methenyl-tetrahydrofolyl-polyglutamate (MTHF) and the catalytic cofactor flavin a

71 nt, which is a 5,10-methenyltetrahydrofolate polyglutamate (MTHF) in most cases.

72 here was a significant decrease in the total polyglutamated MTX in the gut in the GLN group.

73 the mechanism for higher accumulation of MTX polyglutamates (MTX-PG) in hyperdiploid ALL and lower ac

74 Intracellular methotrexate (MTX) polyglutamates (MTXGlu) have been shown to be potentiall

75 assessed by measuring concentrations of MTX polyglutamates (MTXGlu), has been demonstrated to be a p

76 To determine whether higher MTX polyglutamate (MTXPG) concentrations in ALL blasts trans

77 of leukemia cells to accumulate methotrexate polyglutamate (MTXPG) is an important determinant of the

78 ith significantly higher accumulation of MTX polyglutamates (MTXPG(4-7)) in ALL cells.

79 ular metabolism of methotrexate (MTX) to MTX-polyglutamates (MTXPG) is one determinant of cytotoxicit

80 f its effects through polyglutamation to MTX polyglutamates (MTXPGs) and inhibition of 5-aminoimidazo

81 od cell (RBC) concentrations of methotrexate polyglutamates (MTXPGs) and thioguanine nucleotides (TGN

82 Methotrexate polyglutamates (MTXPGs) determine in vivo efficacy in ac

83 Cellular accumulation of methotrexate polyglutamates (MTXPGs) is recognized as an important de

84 Soy-based formulas contained polyglutamates of 5-formyl-tetrahydrofolate.

85 he bacterial synthesis yielded predominantly polyglutamates of [(3)H]5-methyltetrahydrofolate and [(3

86 ximal gamma-glutamyl linkage of longer chain polyglutamates of folates and their analogues.

87 c leukemia blasts accumulate less long chain polyglutamates of methotrexate (MTX) than acute lymphocy

88 se (GGH) catalyzes degradation of the active polyglutamates of natural folates and the antifolate met

89 The effects of LY231514 and its polyglutamates on aminoimidazole carboxamide ribonucleot

90 n, we tested the ability of polyaspartate or polyglutamate peptides to block the binding of ligands t

91 lic acid exposure was in the form of dietary polyglutamates rather than the more easily absorbed supp

92 5-formyl- and 5,10-methenyltetrahydrofolate polyglutamates, respectively.

93 n of thioguanine nucleotides or methotrexate polyglutamates, respectively.

94 yglutamates and 1.5 and 4.5 nmol/L for total polyglutamates, respectively.

95 rboxypeptidase (CCP) family that metabolizes polyglutamate side chain and its loss results in neurode

96 mylation, where they catalyze the removal of polyglutamate side chains.

97 rrier but, unlike 1, is independent of folyl polyglutamate synthase (FPGS) expression levels and poly

98 , including folate hydrolase (FOLH1), folate polyglutamate synthase (FPGS), gamma-glutamyl hydrolase

99 ells, respectively, because of decreased MTX polyglutamate synthesis (despite having similar levels o

100 ing a mechanism for the regulation of folate polyglutamate synthesis in cells.

101 ediated in vivo by the cellular enzyme folyl polyglutamate synthetase.

102 e cytoplasmic SHMT (cSHMT), lacking only the polyglutamate tail of the inhibitor, has been determined

103 olism and are predominantly decorated with a polyglutamate tail that enhances co-enzyme affinity, sub

104 sidues that contribute to the binding of the polyglutamate tail.

105 brain microtubules is suspected to occur via polyglutamates that are added post-translationally to tu

106 that 3 and its B-ring analogues cannot form polyglutamates, their high cytotoxicity relative to the

107 in regard to i) digestion of dietary folate polyglutamates to folate monoglutamates by the cloning o

108 The relative contribution of polyglutamates to the total folate content remained low

109 data demonstrate that BCRP is a MTX and MTX-polyglutamate transporter and reveal a possible mechanis

110 5-Methyltetrahydrofolate polyglutamates were the only folate form found in RBCs f

111 glutamates and 5,10-methenyltetrahydrofolate polyglutamates, which were also major forms of folate in