Exploring a multivalent approach to α-L-fucosidase inhibition

Elena Moreno-Clavijo; Ana T. Carmona; Antonio J. Moreno-Vargas; Lidia Molina; Daniel W. Wright; Gideon J. Davies; Inmaculada Robina

doi:10.1002/ejoc.201300878

Exploring a multivalent approach to α-L-fucosidase inhibition

Elena Moreno-Clavijo, Ana T. Carmona, Antonio J. Moreno-Vargas, Lidia Molina, Daniel W. Wright, Gideon J. Davies, Inmaculada Robina^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

To probe the utility of a multivalent approach for fucosidase inhibition, a series of di- and tri-valent imino sugars based on L-fuco-configured 1,4-imino- and 1,4-bis(imino)-cyclitol epitopes has been synthesized and analyzed for fucosidase inhibition with the best trivalent species yielding a modest improvement in binding constant. Structural analysis of a representative pair of mono- and tri-valent imino sugars has been performed on a bacterial fucosidase, BtFuc2970. The 3D structures show binding of the imino-cyclitol in the ³E conformation, consistent with the known pathway for fucosidase action. Di- and tri-valent imino sugars based on L-fuco-configured 1,4-imino- and 1,4-bis(imino)-cyclitol moieties present α-L-fucosidase inhibitory activities in the μM and nM range.

Original language	English
Pages (from-to)	7328-7336
Number of pages	9
Journal	European Journal of Organic Chemistry
Issue number	32
Early online date	19 Sept 2013
DOIs	https://doi.org/10.1002/ejoc.201300878
Publication status	Published - 10 Oct 2013

Keywords

Carbohydrates
Enzymes
Glycoconjugates
Imino sugars
Inhibitors
Structure-activity relationships

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10.1002/ejoc.201300878

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title = "Exploring a multivalent approach to α-L-fucosidase inhibition",

abstract = "To probe the utility of a multivalent approach for fucosidase inhibition, a series of di- and tri-valent imino sugars based on L-fuco-configured 1,4-imino- and 1,4-bis(imino)-cyclitol epitopes has been synthesized and analyzed for fucosidase inhibition with the best trivalent species yielding a modest improvement in binding constant. Structural analysis of a representative pair of mono- and tri-valent imino sugars has been performed on a bacterial fucosidase, BtFuc2970. The 3D structures show binding of the imino-cyclitol in the 3E conformation, consistent with the known pathway for fucosidase action. Di- and tri-valent imino sugars based on L-fuco-configured 1,4-imino- and 1,4-bis(imino)-cyclitol moieties present α-L-fucosidase inhibitory activities in the μM and nM range.",

keywords = "Carbohydrates, Enzymes, Glycoconjugates, Imino sugars, Inhibitors, Structure-activity relationships",

author = "Elena Moreno-Clavijo and Carmona, {Ana T.} and Moreno-Vargas, {Antonio J.} and Lidia Molina and Wright, {Daniel W.} and Davies, {Gideon J.} and Inmaculada Robina",

year = "2013",

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doi = "10.1002/ejoc.201300878",

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AU - Moreno-Clavijo, Elena

AU - Carmona, Ana T.

AU - Moreno-Vargas, Antonio J.

AU - Molina, Lidia

AU - Wright, Daniel W.

AU - Davies, Gideon J.

AU - Robina, Inmaculada

PY - 2013/10/10

Y1 - 2013/10/10

N2 - To probe the utility of a multivalent approach for fucosidase inhibition, a series of di- and tri-valent imino sugars based on L-fuco-configured 1,4-imino- and 1,4-bis(imino)-cyclitol epitopes has been synthesized and analyzed for fucosidase inhibition with the best trivalent species yielding a modest improvement in binding constant. Structural analysis of a representative pair of mono- and tri-valent imino sugars has been performed on a bacterial fucosidase, BtFuc2970. The 3D structures show binding of the imino-cyclitol in the 3E conformation, consistent with the known pathway for fucosidase action. Di- and tri-valent imino sugars based on L-fuco-configured 1,4-imino- and 1,4-bis(imino)-cyclitol moieties present α-L-fucosidase inhibitory activities in the μM and nM range.

AB - To probe the utility of a multivalent approach for fucosidase inhibition, a series of di- and tri-valent imino sugars based on L-fuco-configured 1,4-imino- and 1,4-bis(imino)-cyclitol epitopes has been synthesized and analyzed for fucosidase inhibition with the best trivalent species yielding a modest improvement in binding constant. Structural analysis of a representative pair of mono- and tri-valent imino sugars has been performed on a bacterial fucosidase, BtFuc2970. The 3D structures show binding of the imino-cyclitol in the 3E conformation, consistent with the known pathway for fucosidase action. Di- and tri-valent imino sugars based on L-fuco-configured 1,4-imino- and 1,4-bis(imino)-cyclitol moieties present α-L-fucosidase inhibitory activities in the μM and nM range.

KW - Carbohydrates

KW - Enzymes

KW - Glycoconjugates

KW - Imino sugars

KW - Inhibitors

KW - Structure-activity relationships

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JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

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ER -

Exploring a multivalent approach to α-L-fucosidase inhibition

Abstract

Keywords

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