STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
发明人:
HUIB OVAA,FARID EL OUALID,MONIQUE MULDER
申请号：
NL2013366
公开号：
NL2013366B1
申请日:
2014.08.26
申请国别(地区):
NL
年份:
2016
代理人:
摘要：
The present invention concerns compounds that are capable of covalently entrapping adenylating enzymes. The present invention is essentially based on the discovery that analogues of adenylating enzyme (AE) substrates, wherein a methylene group has been incorporated at the carbon atom in the α-position relative to the carboxylate group involved in the adenylation, are capable of undergoing the adenylation reaction, thereby creating an activated methylene group in situ. The resulting armed acyladenylate can interact with the enzyme resulting in covalent entrapment. Interestingly, the acyladenylate can alternatively be transferred to the next step in the enzyme cascade, following which the activated methylene group can interact with the next (active site cysteine containing) enzyme in the enzymatic cascade. The AE substrate analogues, based on their capability of entrapping the respective enzymes, will have utility as activity based probes in biological research and also as diagnostic and/or therapeutic agents.
