ライフサイエンスコーパス: sLe(X)

1 Additionally, sLeX(+)CD4(+)T cells exclusively contain the regulatory

2 mon resonance experiments determined that an sLe(X) analogue (TBC1269) competitively inhibited, via s

3 tennary N-glycans, and 3) reduced LacNAc and sLe(X) on N-glycans and on core 2 O-glycans.

4 tin ligand expression and related LacNAc and sLe(X) structures, MALDI-TOF and MALDI-TOF/TOF mass spec

5 canonical ligands sialyl-Lewis A (sLeA) and sLeX mediate particularly high-affinity E-selectin bindi

6 Based on anti-sLe(X) antibody and lectin probing experiments on 4-F-Gl

7 Unlike anti-sLe(X) mAbs, CHO-131 binding also indicates C2GnT activi

8 These results indicate that P-selectin binds sLeX in a shallow cleft that is similar to the mannose-b

9 nal N-acetylglucosamine residue also blocked sLe(X) formation in cells.

10 functional studies, we find that human blood sLeX(+)CD4(+)T cells comprise a subpopulation expressing

11 een implicated in P-selectin binding to both sLeX and 3-sulfated galactosylceramide (sulfatide).

12 man RBCs showed dose-dependent inhibition by sLeX.

13 Among CD8(+)T cells, sLeX expression distinguishes a subset displaying low ex

14 n wall shear stress within the flow chamber, sLe(X)/aICAM-1 microsphere site density, and P-selectin/

15 inguished by the mAb HECA-452, which detects sLe(X)-related glycans.

16 ll proportion of human blood T cells express sLeX, and their function is not fully defined.

17 sion on P-selectin, only peptides expressing sLe(X) groups showed rolling adhesion on E-selectin.

18 Although all peptides expressing sLe(X), tyr-SO(3), or both supported some form of rollin

19 Similar binding kinetics are expected for sLe(X)-selectin interactions.

20 emolytic activity and a reduced affinity for sLeX.

21 The lectin domain responsible for sLeX binding is in domain 4 of Ply, which contains candi

22 lectin-carbohydrate binding specificity from sLeX to oligomannose.

23 Furthermore, sLeX(+)CD8(+)T cells present a pattern of features consi

24 eu5Acalpha2-3Galbeta1-4(Fucalpha1-3) GlcNAc; sLe(X)) in tumor cells.

25 ycans released from 4-F-GlcNAc-treated human sLe(X) (+) T cells and leukemic KG1a cells.

26 if this oligosaccharide lacked fucose or if sLe(X) was extended from a core 1 branch.

27 ermediate for downstream enzymes involved in sLe(X) assembly, and (iii) generation of several glycans

28 The last step in sLe(X) biosynthesis is the alpha1,3-fucosyltrasferase (F

29 e acetylated form of this compound inhibited sLe(X) formation in U937 monocytic leukemia cells, sugge

30 t was hypothesized that 4-F-GlcNAc inhibited sLe(X) formation by incorporating into LacNAc and blocki

31 sialyllactosaminyl glycans convertible into sLe(X) are abundantly expressed on human monocytes yet a

32 tyrosine sulfation (GP1), and one that lacks sLe(X) but has three N-terminal tyr-SO(3) groups (SP3).

33 lectin domain that binds the sialyl LewisX (sLeX) carbohydrate (Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3

34 the highest affinity for the sialyl LewisX (sLeX) structure, with a K(d) of 1.88 x 10(-5) M.

35 -5T-Fuc, that blocks FUT activity and limits sLe(X) presentation on HepG2 cells with an EC(50) in the

36 the consequences of inhibiting FUT-mediated sLe(X) formation.

37 a useful probe that can be used to modulate sLe(X) levels in cells to evaluate the consequences of i

38 The C2-O-sLe(X) motif occurs primarily on sialomucins and has bee

39 o sLe(X) extended from a core 2 branch (C2-O-sLe(X)), but CHO-131 demonstrated no reactivity if this

40 glycan terminated with sialyl Lewis(X) (C2-O-sLe(X)).

41 irst gram scale synthesis of SPPS ready C2-O-sLe(X)-Thr-COOH and enabling the scalable synthesis of G

42 scribe the synthesis of a benzoyl-based C2-O-sLe(X)-Thr-COOH building block devoid of any aglycone tr

43 lable, hydrogenolysis-free synthesis of C2-O-sLe(X)-Thr-COOH was identified by both convergent and or

44 C2-O-sLe(X)-Thr-COOH was synthesized in 10 steps with an over

45 ated sLe(X) en route to a peracetylated C2-O-sLe(X)-Thr-COOH.

46 alternate approach to the peracetylated C2-O-sLe(X)-Thr-COOH.

47 on the disaccharides diverts the assembly of sLe(X) from endogenous cell surface glycoconjugates.

48 ring strategy to inhibit the biosynthesis of sLe(X) in cancer cells using peracetylated 5-thio-L-fuco

49 lycosyltransferases that regulate display of sLe(X) reveal high transcript levels among circulating m

50 ethanol (AcGnG-NM) reduces the expression of sLe(X) and diminishes binding in vitro to selectin-coate

51 roxyl group of the alpha1-3-linked fucose of sLe(X), which may account for the enhanced host cell kil

52 The reduction of sLe(X) by the 4'-deoxy analog also diminished experiment

53 Yet, regulation of sLe(X) and related E-selectin ligand expression in PCa c

54 These compounds represent a novel series of sLe(X) mimetics with antiinflammatory activity.

55 iver-metastatic PCa and dictate synthesis of sLe(X) and E-selectin ligands on metastatic PCa cells.

56 tins with low affinity comparable to that of sLe(X)-selectin interactions.

57 in P-selectin binding to either sulfatide or sLeX.

58 ent [2 + 1 + 1] synthesis of a peracetylated sLe(X) en route to a peracetylated C2-O-sLe(X)-Thr-COOH.

59 distinct PSGL-1 peptides: one that possesses sLe(X) in conjunction with three N-terminal tyr-SO(3) gr

60 tyr-SO(3) groups (SGP3), one that possesses sLe(X) without tyrosine sulfation (GP1), and one that la

61 Monocytes prominently present sLe(X) decorations on an array of protein scaffolds, inc

62 Separately, sLe(X)/P-selectin interactions support rolling and aICAM

63 tant role during selectin recognition, since sLe(X) and sialyl Lewis-a (sLe(a)) were approximately 5-

64 ctin binding at 30-100-fold lower doses than sLe(X).

65 Such analysis predicts that sLe(X) expression varies directly with sialyltransferase

66 Our results show that sLe(X)/aICAM-1 microspheres will firmly adhere to P-sele

67 Together, these findings reveal that sLeX display is associated with unique functional specia

68 Results demonstrate that 1) the sLe(X) (sialyl-Lewis-X) epitope is expressed in P-select

69 s demonstrate an almost complete loss of the sLe(X) epitope on both leukocyte N- and O-glycans.

70 hat mediate the binding of P-selectin to the sLeX carbohydrate have been determined.

71 s showed that blocking binding of Ply to the sLeX glycolipid on RBCs prevents deposition of the toxin

72 archetypal CDC requires interaction with the sLeX glycolipid cellular receptor as an essential step b

73 CHO-131 bound to sLe(X) extended from a core 2 branch (C2-O-sLe(X)), but

74 3) The activity of enzymes contributing to sLe(X) formation in leukocytes likely varies as ST3[Galb

75 the assembly of oligosaccharides related to sLe(X) synthesis, and the assembly of oligosaccharides o

76 ii) generation of several glycans related to sLe(X).

77 f aICAM-1/ICAM-1 interaction is greater when sLe(X)/P-selectin interactions are present.

78 e-sulfated, in addition to glycosylated with sLe(X), to successfully interact with P-selectin.

79 We show that P-selectin's interaction with sLe(X) mechanistically facilitates firm adhesion mediate

80 Thus, interfering with sLe(X) assembly might provide a chemotherapeutic method

81 selectin binding determinant sialyl Lewis X (sLe(X)) and display markedly greater adhesive interactio

82 2 O-glycans terminated with sialyl-Lewis x (sLe(X)) are functionally important oligosaccharides that

83 crement of host-cell-surface sialyl Lewis X (sLe(X)) exacerbates the killing by several wild-type IAV

84 Sialyl-Lewis X (sLe(X)) is a tetrasaccharide that serves as a ligand for

85 Sialyl Lewis X (sLe(X)) on prostate cancer (PCa) cells is thought to pro

86 Clustered presentation of sialyl Lewis X (sLe(X)) on tumor cell mucins is thought to facilitate me

87 -acetyllactosamine (LacNAc), sialyl Lewis X (sLe(X)), and related lectin ligands on effector leukocyt

88 P- and L-selectin binding to sialyl Lewis X (sLe(X))-containing ligands, and the myosin-actin motor p

89 le oligosaccharides based on sialyl Lewis-X (sLe(X)) and complex molecules with the core-2 structure

90 (Galbeta1,4GlcNAc) to create sialyl Lewis-X (sLe(X)) and related sialofucosylated glycans on human le

91 ate the presence of both the sialyl Lewis-X (sLe(X)) and the di-sialylated T-antigen (NeuAcalpha2,3Ga

92 pate in the formation of the sialyl Lewis-X (sLe(X)) epitope on O-glycans linked to a leukocyte cell-

93 bonds in the pentasaccharide sialyl Lewis-X (sLe(X)-5) between 5 and 37 degrees C in water.

94 , FUT3, which contributes to sialyl Lewis X (sLeX) production, is preferentially expressed in the non

95 Sialyl Lewis X (sLeX) regulates T cell trafficking from the vasculature

96 d with the selectin ligand, sialyl Lewis(X) (sLe(X)), and an antibody against ICAM-1, aICAM-1, are pe

97 pies of the tetrasaccharide sialyl-Lewis(x) (sLe(X)), as well as a cluster of three tyrosine sulfate