Small-molecules that covalently react with a human prolyl hydroxylase – towards activity modulation and substrate capture

We describe covalently binding modulators of the activity of human prolyl hydroxylase domain 2 (PHD2) and studies towards a strategy for photocapture of PHD2 substrates. Reversible active site binding of electrophile bearing compounds enables susbsequent covalent reaction with a lysine residue (K408...

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Detalles Bibliográficos
Main Authors: Bush, J, Lesniak, R, Yeh, T, Belle, R, Kramer, H, Tumber, A, Chowdhury, R, Flashman, E, Mecinovic, J, Schofield, C
Formato: Journal article
Publicado: Royal Society of Chemistry 2018
Descripción
Summary:We describe covalently binding modulators of the activity of human prolyl hydroxylase domain 2 (PHD2) and studies towards a strategy for photocapture of PHD2 substrates. Reversible active site binding of electrophile bearing compounds enables susbsequent covalent reaction with a lysine residue (K408) in the flexible C-terminal region of PHD2 to give a modified protein that retains catalytic activity.