Molecular recognition. III. The binding of the H-type 2 human blood group determinant by the lectin I of <i>Ulex</i><i>europaeus</i>

Hindsgaul, Ole; Khare, Deveshwari P.; Bach, Mimi; Lemieux, R. U.

doi:10.1139/v85-440

Cited by 87 publications

(63 citation statements)

References 8 publications

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“…The acceptance of intramolecularly hydrogen-bonded molecules into nonpolar regions in the combining site and the interaction of water molecules with the amphypatic surfaces of oligosaccharides to provide a driving force for complex formation have been extensively discussed by Lemieux [l,21. These nonpolar interactions seem to be operative in most of the complexes between oligosaccharides and lectins or antibodies investigated to date [7,[67][68][69][70][71][72]. The presence of a bulky methyl group at position 3 (compound 5), which precludes hydrogen-bond formation and imposes a steric destabilization results in a decreasing of the strength of the binding.…”

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confidence: 99%

Studies on the molecular recognition of synthetic methyl β‐lactoside analogs by ricin, a cytotoxic plant lectin

Rivera‐Sagredo

Solı́s

Dı́az-Mauriño

et al. 1991

European Journal of Biochemistry

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The binding of methyl P-lactoside and of all possible monodeoxy derivatives of methyl P-lactoside to the galactose-specific highly cytotoxin lectin ricin, has been investigated. The distribution of low-energy conformers of the disaccharide structures has been first determined using molecular-mechanics calculations and high-resolution NMR spectroscopy. The nuclear Overhauser enhancements and specific deshieldings observed are in agreement with a similar distribution of low-energy conformers for all studied compounds which may be described by a major conformer defined by cp (H1'-C1'-01'-C4) and w (Cl'-Ol'-C4-H4) torsion angles of 49" and 5", respectively, with contribution of conformers with angles cp/w 24"/ -59", 22"/ -32 " and 6"/ -44". Assuming that the disaccharides bind to the lectin in these preferred conformations, the apparent dissociation constants for the ricindisaccharide complexes have been interpreted in terms of specific polar and nonpolar interactions. In agreement with X-ray data, the hydroxyl groups at positions 3, 4 and 6 of the P-D-galactopyranose moiety appear as key polar groups in the interaction with ricin. These results are in contrast to previous results which have established that position 6 is not involved in lectin binding. An important nonpolar interaction involving position 3 of the P-D-glucopyranose moiety, seems to be operative. The distribution of low-energy conformers of these disaccharide structures permits this interaction to take place with the hydroxyl group at this position intramolecularly bonded, thus rendering this region of the molecule more lipophylic in character for acceptance into nonpolar regions of the combining site.The origin of the specificity observed in the molecular recognition of carbohydrates by lectins and antibodies has been suggested to include crucial polar interactions, involving a cluster of two or more hydroxyl groups, and short range multipoint van der Waals interactions between complementary nonpolar surfaces. These nonpolar interactions would play an important role on the setting of the stability of the complex while polar interactions within the combining site would be the key to complex formation [I, 21. On the basis of highly refined X-ray structures of some carbohydrate-protein complexes it has been concluded that both hydrogen bonds and van der Waals contacts are indeed the dominant forces that stabilize carbohydrate-protein interactions, although it has been anticipated that the former would provide the major contributions to the binding [3, 41. Binding studies with synthetic carbohydrate molecules having a range of slightly modified structures have proved extremely fruitful to probe the combining site [I, 2, 5-91, A proper interpretation of the results from these studies together with highly refined crystallographic data may be of paramount importance to achieve an appreciation of the origin of the specific interactions.This paper is concerned with the molecular recognition of synthetic methyl P-lactoside analogs by ricin, the highly Ricin i...

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confidence: 99%

Studies on the molecular recognition of synthetic methyl β‐lactoside analogs by ricin, a cytotoxic plant lectin

Rivera‐Sagredo

Solı́s

Dı́az-Mauriño

et al. 1991

European Journal of Biochemistry

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“…Judging from the shapes of the topographies provided by the oligosaccharide to the complex, the polar interactions within the complex occur at the interface with the aqueous environment. This matter was previously discussed in relation to the binding of the H-type 2 determinant by the lectin I of Ulex europaeus (6). Definitely, the interaction between the nonpolar complementary surfaces contributes importantly and, indeed, appears to be the dominating factor for complex stability (6).…”

Section: Resultsmentioning

confidence: 92%

“…This matter was previously discussed in relation to the binding of the H-type 2 determinant by the lectin I of Ulex europaeus (6). Definitely, the interaction between the nonpolar complementary surfaces contributes importantly and, indeed, appears to be the dominating factor for complex stability (6). Considering that the polar interactions, which are directional in character, must be compatible with the required orientations for the complementary lipophilic surfaces to interact, it is evident that these interactions provide the main contribution to the specificity of the overall binding reaction.…”

Section: Resultsmentioning

confidence: 96%

“…The data in Table 1 require that neither OH-6" nor OH-6' are involved in polar interactions within the combining sites, since the replacement of these hydroxyls by hydrogen provided highly active compounds (5 and 6). Because the 6'-deoxy derivative (6) is a superior inhibitor, it is anticipated that 1 is bound with OH-6' intramolecularly hydrogen bonded to 0-5', as is present in the crystal structure (IS), a situation that was observed both for the binding of the H-type 2 determinant of Ulex europaeus (6,19) and the Lewis b determinant by a hybridoma monoclonal anti-Leb antibody (7). That binding occurs about the C-6' grouping is required by the low activity of the PL Ara compound 24.…”

Section: Resultsmentioning

confidence: 99%

“…The conformation of 1 places the key polar grouping adjacent to this lipophilic surface. As in all cases so far studied (5)(6)(7)(8), this polar grouping is well positioned to interact with a polar grouping at the periphery of the combining site and termed the polar gate (20). Prior to binding, both the polar groupings (i.e., the key and the gate) likely are strongly hydrated and their interaction may not contribute importantly to the stability of the complex.…”

Section: Resultsmentioning

confidence: 99%

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Molecular recognition. V. The binding of the B human blood group determinant by hybridoma monoclonal antibodies

Lemieux¹,

Venot²,

Spohr³

et al. 1985

Can. J. Chem.

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A systematic study was made of the effect of changes in the structure of αLFuc(1→2)[αDGal(1→3)]βDGal-OMe (1) on the inhibition of the binding of an artificial antigen by two monoclonal anti-B antibodies. Both OH-4 of the βDGal unit and OH-2 of the αDGal unit are essential for binding by one of the antibodies. For the other antibody, OH-3 of the αDGal unit also forms part of the key polar grouping. Both the antibodies recognize a large lipophilic surface extending from the CH3-6 group of the αLFuc unit along the α-sides of this group and the βDGal unit to include its CH2OH-6 group, most likely intramolecularly hydrogen bonded to the neighboring O-5. The lipophilic surface then extends to include the CH2OH-6 group of the αDGal unit intramolecularly hydrogen bonded to the O-5 atom. The stability of the complex is attributed to nonpolar interaction of this surface within a hydrophobic cleft-like combining site which offers a polar grouping at its periphery for interaction with the key polar grouping of the trisaccharide. The solution conformer for 1, as determined by 1H nmr, is present in its crystal structure.

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Localisation of glycans in the placenta: A comparative study of epitheliochorial, endotheliochorial, and haemomonochorial placentation

Jones

Dantzer²,

Leiser

et al. 1997

Microsc. Res. Tech.

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Molecular recognition. III. The binding of the H-type 2 human blood group determinant by the lectin I of Ulexeuropaeus

Cited by 87 publications

References 8 publications

Studies on the molecular recognition of synthetic methyl β‐lactoside analogs by ricin, a cytotoxic plant lectin

Studies on the molecular recognition of synthetic methyl β‐lactoside analogs by ricin, a cytotoxic plant lectin

Molecular recognition. V. The binding of the B human blood group determinant by hybridoma monoclonal antibodies

Localisation of glycans in the placenta: A comparative study of epitheliochorial, endotheliochorial, and haemomonochorial placentation

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