Vom E-Selektin-Liganden 1 abgeleitete Glycopeptide mit variierter Sialyl-Lewisx-Struktur als Zelladhäsionsinhibitoren für E-Selektin

Synthetic Glycopeptides from the E-Selectin Ligand 1 with Varied Sialyl Lewisx Structure as Cell-Adhesion Inhibitors of E-Selectin.

Synthetic Inhibitors of Cell Adhesion: A Glycopeptide from E-Selectin Ligand 1 (ESL-1) with the Arabino Sialyl Lewisx Structure

Particularly selective methods are required for the synthesis of arabino sialyl Lewisx glycopeptides owing to the acid-labile β-arabinopyranoside bond. It is important for the inhibition of cell adhesion that the arabino sialyl Lewisx glycopeptide 1, which contains the Gly 672 -Asp 681 sequence of the E-selectin Ligand 1 (ESL-1), binds ten times more strongly than sialyl Lewisx to E-selectin, although it is monovalent and does not contain L-fucose, which is considered essential.

Sulfated and Non-Sulfated Glycopeptide Recognition Domains of P-Selectin Glycoprotein Ligand 1 and their Binding to P- and E-Selectin

Total synthesis through block glycosylation and selective chemical O-sulfation of tyrosine residues yielded the glycopeptide recognition domain A (X=SO(3) (-)) of the P-selectin glycoprotein ligand 1, in which the terminal sialic acid of the complex hexasaccharide side chain was replaced by (S)-cyclohexyl lactic acid. In binding assays the O-sulfated structure A showed high affinity towards P-selectin, the non-sulfated towards E-selectin.

Sulfatierte und nicht sulfatierte Glycopeptid-Erkennungsdomänen des P-Selektin-Glycoprotein-Liganden 1 und ihre Bindung an P- und E-Selektin

Totalsynthese via Blockglycosylierung und selektive chemische O-Sulfatierung von Tyrosinresten ergaben die Glycopeptid-Erkennungsregion A (X=SO3−) des P-Selektin-Glycoprotein-Liganden 1, in dem die terminale Sialinsaure der komplexen Hexasaccharid-Seitenkette durch (S)-Cyclohexylmilchsaure als Mimetikum ersetzt ist. In Bindungsassays zeigt die O-sulfatierte Form A hohe Affinitat zu P-Selektin, die nicht sulfatierte Form zu E-Selektin.

Synthetische Inhibitoren der Zelladhäsion: ein Glycopeptid aus dem E-Selektin-Liganden 1 (ESL-1) mit Arabino-Sialyl-Lewisx-Struktur

ChemInform Abstract: Synthetic Inhibitors of Cell Adhesion: A Glycopeptide from E-Selectin Ligand 1 (ESL-1) with the Arabino Sialyl Lewisx Structure.

LFA-1 Contributes to Signal I of T-Cell Activation and to the Production of Th1 Cytokines

The beta(2) integrins are important for both transendothelial migration of leukocytes and T-cell activation during antigen presentation. In T cells, triggering of leukocyte functional antigen-1 (LFA-1) is required for full activation and T-helper (Th)1/Th2 differentiation. We used CD18-deficient (CD18(-/-)) mice to examine the role of LFA-1 in the activation of T cells. Compared with wild-type controls, CD18(-/-) T cells proliferated normally when stimulated with antibodies against CD3 and CD28, but secreted significantly less IFN-gamma and IL-2 than their wild-type counterparts. However, when T cells were stimulated with dendritic cells (DCs) that provide additional LFA-1 ligation, the pro…