A small molecule glycosaminoglycan mimetic blocks Plasmodium invasion of the mosquito midgut

Derrick K Mathias; Rebecca Pastrana-Mena; Elisabetta Ranucci; Dingyin Tao; Paolo Ferruti; Corrie Ortega; Gregory O Staples; Joseph Zaia; Eizo Takashima; Takafumi Tsuboi; Natalie Borg; Luisella Verotta; Rhoel R Dinglasan

doi:10.1371/journal.ppat.1003757

A small molecule glycosaminoglycan mimetic blocks Plasmodium invasion of the mosquito midgut

Derrick K Mathias, Rebecca Pastrana-Mena, Elisabetta Ranucci, Dingyin Tao, Paolo Ferruti, Corrie Ortega, Gregory O Staples, Joseph Zaia, Eizo Takashima, Takafumi Tsuboi, Natalie Borg, Luisella Verotta, Rhoel R Dinglasan

Biochemistry & Molecular Biology

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

20 Citations (Scopus)

Abstract

Malaria transmission-blocking (T-B) interventions are essential for malaria elimination. Small molecules that inhibit the Plasmodium ookinete-to-oocyst transition in the midgut of Anopheles mosquitoes, thereby blocking sporogony, represent one approach to achieving this goal. Chondroitin sulfate glycosaminoglycans (CS-GAGs) on the Anopheles gambiae midgut surface are putative ligands for Plasmodium falciparum ookinetes. We hypothesized that our synthetic polysulfonated polymer, VS1, acting as a decoy molecular mimetic of midgut CS-GAGs confers malaria T-B activity. In our study, VS1 repeatedly reduced midgut oocyst development by as much as 99 (P

Original language	English
Article number	e1003757
Number of pages	14
Journal	PLoS Pathogens
Volume	9
Issue number	11
DOIs	https://doi.org/10.1371/journal.ppat.1003757
Publication status	Published - 2013

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Cite this

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abstract = "Malaria transmission-blocking (T-B) interventions are essential for malaria elimination. Small molecules that inhibit the Plasmodium ookinete-to-oocyst transition in the midgut of Anopheles mosquitoes, thereby blocking sporogony, represent one approach to achieving this goal. Chondroitin sulfate glycosaminoglycans (CS-GAGs) on the Anopheles gambiae midgut surface are putative ligands for Plasmodium falciparum ookinetes. We hypothesized that our synthetic polysulfonated polymer, VS1, acting as a decoy molecular mimetic of midgut CS-GAGs confers malaria T-B activity. In our study, VS1 repeatedly reduced midgut oocyst development by as much as 99 (P",

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AU - Mathias, Derrick K

AU - Pastrana-Mena, Rebecca

AU - Ranucci, Elisabetta

AU - Tao, Dingyin

AU - Ferruti, Paolo

AU - Ortega, Corrie

AU - Staples, Gregory O

AU - Zaia, Joseph

AU - Takashima, Eizo

AU - Tsuboi, Takafumi

AU - Borg, Natalie

AU - Verotta, Luisella

AU - Dinglasan, Rhoel R

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UR - http://www.ncbi.nlm.nih.gov/pubmed/24278017

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A small molecule glycosaminoglycan mimetic blocks Plasmodium invasion of the mosquito midgut

Abstract

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