Kohlenhydratmimetika: ein neuer Lösungsansatz für das Problem der kohlenhydratvermittelten biologischen Erkennung

Sears, P.S.; Wong, Chi‐Huey

doi:10.1002/(sici)1521-3757(19990816)111:16<2446::aid-ange2446>3.0.co;2-4

Cited by 89 publications

(24 citation statements)

References 191 publications

(154 reference statements)

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“…Oligosaccharides offer great potential as therapeutic agents, [1,2] and much research has been directed towards the synthesis and evaluation of enzyme inhibitors both as mechanistic and structural probes and for clinical assessment. In order to utilise multiple binding sites for oligo-and polysaccharide-degrading enzymes, inhibitors must span the catalytic centre of the enzyme, avoiding enzymatic hydrolysis whilst ideally also accommodating potential substrate distortion in the À 1 site (subsite nomenclature reviewed in ref.…”

Section: Introductionmentioning

confidence: 99%

Mixed-Linkage Cellooligosaccharides: A New Class of Glycoside Hydrolase Inhibitors

et al. 2001

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A new class of inhibitors for beta-D-glycoside hydrolases, in which a single alpha-(1-->4)-glycosidic bond is incorporated into an otherwise all-beta-(1-->4)-linked oligosaccharide, is described. Such mixed beta/alpha-linkage cellooligosaccharides are not transition-state mimics, but instead are capable of utilising binding energy from numerous subsites, spanning either side of the catalytic centre, without the need for substrate distortion. This binding is significant; a mixed alpha/beta-D-tetrasaccharide acts competitively on a number of cellulases, displaying inhibition constants in the range of 40-300 microM. Using the Bacillus agaradhaerens enzyme Cel5A as a model system, one such mixed beta/alpha-cellooligosaccharide, methyl 4(II),4(III)-dithio-alpha-cellobiosyl-(1-->4)-beta-cellobioside, displays a K(i) value of 100 microM, an inhibition at least 150 times better than is observed with an equivalent all-beta-linked compound. The three-dimensional structure of B. agaradhaerens Cel5A in complex with methyl 4(II),4(III)-dithio-alpha-cellobiosyl-(1-->4)-beta-cellobioside has been determined at 1.8 A resolution. This confirms the expected mode of binding in which the ligand, with all four pyranosides in the (4)C(1) chair conformation, occupies the -3, -2 and +1 subsites whilst evading the catalytic (-1) subsite. Such "by-pass" compounds offer great scope for the development of a new class of beta-D-glycoside hydrolase inhibitors.

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Section: Introductionmentioning

confidence: 99%

Mixed-Linkage Cellooligosaccharides: A New Class of Glycoside Hydrolase Inhibitors

et al. 2001

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“…When the geometry of crucial groups is maintained or even improved, the obtained substances do not even need to belong to the class of carbohydrates. To grant adequate heed to mimetics is probably a means to open a wide field for rational drug design, currently, for example, exploited for the influenza A/B neuraminidase and selectins (Sears and Wong, 1999;Simanek et al, 1998;von Itzstein and Thomson, 1997). As caveats to caution against prematurely advocating clinical effectiveness of anti-adhesion therapy in inflammation or of sugar-based drugs in epidemic flu, detrimental long-term effects in an animal model mimicking both acute and chronic intestinal inflammation has been reported (McCafferty et al, 1999).…”

Section: How To Define Potent Ligand Mimeticsmentioning

confidence: 99%

The Codes of Life

Barbieri¹,

Hoffmeyer²

2008

Biosemiotics

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Aims and Scope of the SeriesCombining research approaches from biology, philosophy and linguistics, the emerging field of biosemiotics proposes that animals, plants and single cells all engage in semiosis -the conversion of physical signals into conventional signs. This has important implications and applications for issues ranging from natural selection to animal behaviour and human psychology, leaving biosemiotics at the cutting edge of the research on the fundamentals of life.The Springer book series Biosemiotics draws together contributions from leading players in international biosemiotics, producing an unparalleled series that will appeal to all those interested in the origins and evolution of life, including molecular and evolutionary biologists, ecologists, anthropologists, psychologists, philosophers and historians of science, linguists, semioticians and researchers in artificial life, information theory and communication technology.

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“…In a series of publications [1–6] our group reported on the syntheses of carbohydrate mimetics [7–11] that are based on aminopyrans, aminooxepanes or other aminopolyols. These compounds and their conjugates were prepared to be examined as selectin inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors

Salta¹,

Dernedde²,

Reißig³

2015

Beilstein J. Org. Chem.

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SummaryIn this article a series of divalent and trivalent carbohydrate mimetics on the basis of an enantiopure aminopyran and of serinol is described. These aminopolyols are connected by amide bonds to carboxylic acid derived spacer units either by Schotten–Baumann acylation or by coupling employing HATU as reagent. The O-sulfation employing the SO3·DMF complex was optimized. It was crucial to follow this process by 700 MHz 1H NMR spectroscopy to ensure full conversion and to use a refined neutralization and purification protocol. Many of the compounds could not be tested as L-selectin inhibitor by SPR due to their insolubility in water, nevertheless, a divalent and a trivalent amide showed surprisingly good activities with IC50 values in the low micromolar range.

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Kohlenhydratmimetika: ein neuer Lösungsansatz für das Problem der kohlenhydratvermittelten biologischen Erkennung

Cited by 89 publications

References 191 publications

Mixed-Linkage Cellooligosaccharides: A New Class of Glycoside Hydrolase Inhibitors

Mixed-Linkage Cellooligosaccharides: A New Class of Glycoside Hydrolase Inhibitors

The Codes of Life

Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors

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