Proteomics

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Development of chemical proteomics for the folateome and analysis of the kinetoplastid folateome - Part 4


ABSTRACT: In this current study, we aimed to produce and develop an affinity matrix for enzymes involved in the folate metabolism of kinetoplastids, effectively the “folateome”folateome of these parasites. This information will then be used to determine the molecular targets of compounds targeting folate metabolism, and to correlate this to phenotypic responses. To achieve this, a small library of clinical and literature anti-folate compounds were immobilized onto resins and used in “pull-down” experiments with and without test compound present, to ascertain proteins binding specifically to particular resins.8,10-11 While the initial focus of this project was to establish the kinetoplastid folateome, the approach has the potential to be extended to other organisms.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Trypanosoma Brucei

SUBMITTER: Michele Tinti  

LAB HEAD: Ian Gilbert

PROVIDER: PXD010408 | Pride | 2018-10-02

REPOSITORIES: Pride

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Development of Chemical Proteomics for the Folateome and Analysis of the Kinetoplastid Folateome.

Webster Lauren A LA   Thomas Michael M   Urbaniak Michael M   Wyllie Susan S   Ong Han H   Tinti Michele M   Fairlamb Alan H AH   Boesche Markus M   Ghidelli-Disse Sonja S   Drewes Gerard G   Gilbert Ian H IH  

ACS infectious diseases 20180928 10


The folate pathway has been extensively studied in a number of organisms, with its essentiality exploited by a number of drugs. However, there has been little success in developing drugs that target folate metabolism in the kinetoplastids. Despite compounds being identified which show significant inhibition of the parasite enzymes, this activity does not translate well into cellular and animal models of disease. Understanding to which enzymes antifolates bind under physiological conditions and h  ...[more]

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