The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness

M A J  Ferguson; J S  Brimacombe; J R  Brown; A  Crossman; A  Dix; R A  Field; M L S  Guther; K G  Milne; D K  Sharma; T K  Smith

doi:10.1016/S0925-4439(99)00058-7

The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness

M A J Ferguson, J S Brimacombe, J R Brown, A Crossman, A Dix, R A Field, M L S Guther, K G Milne, D K Sharma, T K Smith

Research output: Contribution to journal › Review article › peer-review

127 Citations (Scopus)

Abstract

African sleeping sickness is a debilitating and often fatal disease caused by tsetse fly transmitted African trypanosomes. These extracellular protozoan parasites survive in the human bloodstream by virtue of a dense cell surface coat made of variant surface glycoprotein. The parasites have a repertoire of several hundred immunologically distinct variant surface glycoproteins and they evade the host immune response by antigenic variation. All variant surface glycoproteins are anchored to the plasma membrane via glycosylphosphatidylinositol membrane anchors and compounds that inhibit the assembly or transfer of these anchors could have trypanocidal potential. This article compares glycosylphosphatidylinositol biosynthesis in African trypanosomes and mammalian cells and identifies several steps that could be targets for the development of parasite-specific therapeutic agents. (C) 1999 Elsevier Science B.V. All rights reserved.

Original language	English
Pages (from-to)	327-340
Number of pages	14
Journal	Biochimica et Biophysica Acta - Molecular Basis of Disease
Volume	1455
Issue number	2-3
DOIs	https://doi.org/10.1016/S0925-4439(99)00058-7
Publication status	Published - 8 Oct 1999

Keywords

glycosylphosphatidylinositol
GPI
trypanosome
biosynthesis
glycosyltransferase
VARIANT SURFACE GLYCOPROTEIN
GLYCOSYLPHOSPHATIDYLINOSITOL MEMBRANE ANCHOR
GLYCOSYL-PHOSPHATIDYLINOSITOL ANCHOR
GLYCOINOSITOL PHOSPHOLIPID ANCHOR
N-ACETYLGLUCOSAMINYL-PHOSPHATIDYLINOSITOL
HUMAN-ERYTHROCYTE ACETYLCHOLINESTERASE
ASPARAGINE-LINKED OLIGOSACCHARIDES
TRYPANOSOMA-CRUZI 1G7-ANTIGEN
MOLECULAR-SPECIES ANALYSIS
SACCHAROMYCES-CEREVISIAE

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0925-4439(99)00058-7

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title = "The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness",

abstract = "African sleeping sickness is a debilitating and often fatal disease caused by tsetse fly transmitted African trypanosomes. These extracellular protozoan parasites survive in the human bloodstream by virtue of a dense cell surface coat made of variant surface glycoprotein. The parasites have a repertoire of several hundred immunologically distinct variant surface glycoproteins and they evade the host immune response by antigenic variation. All variant surface glycoproteins are anchored to the plasma membrane via glycosylphosphatidylinositol membrane anchors and compounds that inhibit the assembly or transfer of these anchors could have trypanocidal potential. This article compares glycosylphosphatidylinositol biosynthesis in African trypanosomes and mammalian cells and identifies several steps that could be targets for the development of parasite-specific therapeutic agents. (C) 1999 Elsevier Science B.V. All rights reserved.",

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AU - Ferguson, M A J

AU - Brimacombe, J S

AU - Brown, J R

AU - Crossman, A

AU - Dix, A

AU - Field, R A

AU - Guther, M L S

AU - Milne, K G

AU - Sharma, D K

AU - Smith, T K

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AB - African sleeping sickness is a debilitating and often fatal disease caused by tsetse fly transmitted African trypanosomes. These extracellular protozoan parasites survive in the human bloodstream by virtue of a dense cell surface coat made of variant surface glycoprotein. The parasites have a repertoire of several hundred immunologically distinct variant surface glycoproteins and they evade the host immune response by antigenic variation. All variant surface glycoproteins are anchored to the plasma membrane via glycosylphosphatidylinositol membrane anchors and compounds that inhibit the assembly or transfer of these anchors could have trypanocidal potential. This article compares glycosylphosphatidylinositol biosynthesis in African trypanosomes and mammalian cells and identifies several steps that could be targets for the development of parasite-specific therapeutic agents. (C) 1999 Elsevier Science B.V. All rights reserved.

KW - glycosylphosphatidylinositol

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KW - trypanosome

KW - biosynthesis

KW - glycosyltransferase

KW - VARIANT SURFACE GLYCOPROTEIN

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KW - GLYCOSYL-PHOSPHATIDYLINOSITOL ANCHOR

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KW - HUMAN-ERYTHROCYTE ACETYLCHOLINESTERASE

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KW - TRYPANOSOMA-CRUZI 1G7-ANTIGEN

KW - MOLECULAR-SPECIES ANALYSIS

KW - SACCHAROMYCES-CEREVISIAE

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SN - 0925-4439

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JO - Biochimica et Biophysica Acta - Molecular Basis of Disease

JF - Biochimica et Biophysica Acta - Molecular Basis of Disease

IS - 2-3

ER -

The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness

Abstract

Keywords

UN SDGs

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