Exploring the Interactions of Unsaturated Glucuronides with Influenza Virus Sialidase

Beenu Bhatt; Raphael Boehm; Philip S. Kerry; Jeffrey C. Dyason; Rupert J. M. Russell; Robin J. Thomson; Mark von Itzstein

doi:10.1021/jm301145k

Exploring the Interactions of Unsaturated Glucuronides with Influenza Virus Sialidase

Beenu Bhatt, Raphael Boehm, Philip S. Kerry, Jeffrey C. Dyason, Rupert J. M. Russell, Robin J. Thomson, Mark von Itzstein^*

^*Corresponding author for this work

School of Biology

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

10 Citations (Scopus)

Abstract

A series of C3 O-functionalized 2-acetamido-2-deoxy-Delta(4)-beta-D-glucuronides were synthesized to explore noncharge interactions in subsite 2 of the influenza virus sialidase active site. In complex with A/N8 sialidase, the parent compound (C3 OH) inverts its solution conformation to bind with all substituents well positioned in the active site. The parent compound inhibits influenza virus sialidase at a sub-mu M level; the introduction of small alkyl substituents or an acetyl group at C3 is also tolerated.

Original language	English
Pages (from-to)	8963-8968
Number of pages	6
Journal	Journal of Medicinal Chemistry
Volume	55
Issue number	20
DOIs	https://doi.org/10.1021/jm301145k
Publication status	Published - 25 Oct 2012

Keywords

NEURAMINIDASE INHIBITORS
BIOLOGICAL EVALUATION
ACID-DERIVATIVES
OSELTAMIVIR
ZANAMIVIR
DESIGN
DISCOVERY
A-315675
ANALOGS
BINDING

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title = "Exploring the Interactions of Unsaturated Glucuronides with Influenza Virus Sialidase",

abstract = "A series of C3 O-functionalized 2-acetamido-2-deoxy-Delta(4)-beta-D-glucuronides were synthesized to explore noncharge interactions in subsite 2 of the influenza virus sialidase active site. In complex with A/N8 sialidase, the parent compound (C3 OH) inverts its solution conformation to bind with all substituents well positioned in the active site. The parent compound inhibits influenza virus sialidase at a sub-mu M level; the introduction of small alkyl substituents or an acetyl group at C3 is also tolerated.",

keywords = "NEURAMINIDASE INHIBITORS, BIOLOGICAL EVALUATION, ACID-DERIVATIVES, OSELTAMIVIR, ZANAMIVIR, DESIGN, DISCOVERY, A-315675, ANALOGS, BINDING",

author = "Beenu Bhatt and Raphael Boehm and Kerry, {Philip S.} and Dyason, {Jeffrey C.} and Russell, {Rupert J. M.} and Thomson, {Robin J.} and {von Itzstein}, Mark",

note = "This research was part funded by the MRC.",

year = "2012",

month = oct,

day = "25",

doi = "10.1021/jm301145k",

language = "English",

volume = "55",

pages = "8963--8968",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society (ACS)",

number = "20",

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T1 - Exploring the Interactions of Unsaturated Glucuronides with Influenza Virus Sialidase

AU - Bhatt, Beenu

AU - Boehm, Raphael

AU - Kerry, Philip S.

AU - Dyason, Jeffrey C.

AU - Russell, Rupert J. M.

AU - Thomson, Robin J.

AU - von Itzstein, Mark

N1 - This research was part funded by the MRC.

PY - 2012/10/25

Y1 - 2012/10/25

N2 - A series of C3 O-functionalized 2-acetamido-2-deoxy-Delta(4)-beta-D-glucuronides were synthesized to explore noncharge interactions in subsite 2 of the influenza virus sialidase active site. In complex with A/N8 sialidase, the parent compound (C3 OH) inverts its solution conformation to bind with all substituents well positioned in the active site. The parent compound inhibits influenza virus sialidase at a sub-mu M level; the introduction of small alkyl substituents or an acetyl group at C3 is also tolerated.

AB - A series of C3 O-functionalized 2-acetamido-2-deoxy-Delta(4)-beta-D-glucuronides were synthesized to explore noncharge interactions in subsite 2 of the influenza virus sialidase active site. In complex with A/N8 sialidase, the parent compound (C3 OH) inverts its solution conformation to bind with all substituents well positioned in the active site. The parent compound inhibits influenza virus sialidase at a sub-mu M level; the introduction of small alkyl substituents or an acetyl group at C3 is also tolerated.

KW - NEURAMINIDASE INHIBITORS

KW - BIOLOGICAL EVALUATION

KW - ACID-DERIVATIVES

KW - OSELTAMIVIR

KW - ZANAMIVIR

KW - DESIGN

KW - DISCOVERY

KW - A-315675

KW - ANALOGS

KW - BINDING

U2 - 10.1021/jm301145k

DO - 10.1021/jm301145k

M3 - Article

SN - 0022-2623

VL - 55

SP - 8963

EP - 8968

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 20

ER -

Exploring the Interactions of Unsaturated Glucuronides with Influenza Virus Sialidase

Abstract

Keywords

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