Studies on selectin blocker. 3. Investigation of the carbohydrate ligand sialyl Lewis X recognition site of P-selectin. 1996

Y Hiramatsu, and H Tsujishita, and H Kondo
Department of Medicinal Chemistry, New Drug Research Laboratories, Kanebo Ltd., Osaka, Japan.

We have previously found that a 1-deoxy sialyl Lewis X (3), which lacks only the C-1 hydroxyl group of sialyl Lewis X (sLeX), exhibited up to 20 times more potency than the sLeX toward P-selectin binding. In order to explain the structure-activity relationship, we constructed structural models of the complexes of P-selectin and compounds 1-3 and sLeX. From the modeling analysis, we found that the carbonyl oxygen of the N-acetyl group of GlcNAc in 3 formed a hydrogen bond with the amide group of Asn 82 in P-selectin. We also supposed that there was a hydrophobic interaction between the pyranose of GlcNAc in compound 3 and the imidazole ring of His 108 in P-selectin. However, it is considered that those interactions would not be appreciable in the case of sLeX or other 1-deoxy sLeX analogs (1,2). Accordingly, our results could be helpful in obtaining a new concept to design a potent inhibitor toward P-selectin binding.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009844 Oligosaccharides Carbohydrates consisting of between two (DISACCHARIDES) and ten MONOSACCHARIDES connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. Oligosaccharide
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006860 Hydrogen Bonding A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. Hydrogen Bonds,Bond, Hydrogen,Hydrogen Bond
D000080506 Sialyl Lewis X Antigen A sialylated version of Lewis X antigen expressed on cell surfaces. It is a ligand for SELECTINS. 5-Acetylneuraminyl-(2-3)-Galactosyl-(1-4)-(Fucopyranosyl-(1-3))-N-Acetylglucosamine,CD15s Antigen,Sialyl Le(x),Sialyl Lewis X,Sialyl Lewis(x) Antigen,Sialyl Lewis(x) Tetrasaccharide,Sialyl SSEA-1,Sialyl Stage-Specific Embryonic Antigen-1,Sialyl-Lex,Sialylated Lewis X Antigen,NAG-1,4-F-1,3-GN,Neu5Ac-2-3-Gal-1-4-(Fuc-1-3)-GlcNAc,NeuAcalpha2-3Galbeta1-4(Fucalpha1-3)GlcNAc-R,SLe(x),SLe(x)-OS,alpha-Neu5Ac-(2-3)-beta-D-Gal-(1-4)-(alpha-L-Fuc-(1-3))-beta-D-GlcNAc,Antigen, CD15s,Lewis X, Sialyl,Sialyl Lex,Sialyl SSEA 1,Sialyl Stage Specific Embryonic Antigen 1
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

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