Synthesis and characterisation of substrate-based peptides as inhibitors of histone demethylase KDM4C

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Simon D Nielsen, Ulrike Leurs, Magnus Bergner, Silvia Amor Barris, Kanchan Devkota, Kamilla Meyer, Daniella Iaria, Jack McCaughan, Brian Lohse, Jesper L Kristensen, Rasmus Prætorius Clausen

The design and synthesis of modified pentapeptides based on a truncated version of the substrate for KDM4C, a histone lysine demethylase (KDM), and investigation of their inhibitory activity at KDM4C is reported. By modifying the lysine residue corresponding to lysine 9 at histone 3 (H3K9), three different series of peptides were designed and synthesized. One series contained N-acylated H3K9 and two series introduced triazoles in this position via click chemistry to enable facile variation of headgroups. As the click reaction is compatible with free amino acids this was performed on an azido containing deprotected pentapeptide, thus demonstrating a highly facile and convergent synthetic strategy for making substrate-based inhibitors. One of the 14 peptides showed inhibitory activity at KDM4C demonstrating the need for an iron chelator in the pentapeptide series.

OriginalsprogEngelsk
TidsskriftProtein and Peptide Letters
Vol/bind23
Udgave nummer9
Sider (fra-til)772 - 776
Antal sider5
ISSN0929-8665
DOI
StatusUdgivet - 13 jun. 2016

ID: 162710545