Chemical synthesis and characterization of a new quinazolinedione competitive antagonist for strigolactone receptors with an unexpected binding mode.

Chemical synthesis and characterization of a new quinazolinedione competitive antagonist for strigolactone receptors with an unexpected binding mode. Biochem J. 2019 Jun 11;: Authors: Hamiaux C, Larsen L, Lee HW, Luo Z, Sharma P, Hawkins BC, Perry NB, Snowden KC Abstract Strigolactones are multifunctional plant hormones regulating essential physiological processes affecting growth and development. In vascular plants, strigolactones are recognized by α/β hydrolase fold proteins from the D14/DAD2 family in the initial step of the signalling pathway. We have previously discovered that N -phenylanthranilic acid derivatives (e.g. tolfenamic acid) are potent antagonists of strigolactone receptors, prompting us to design quinazolinone and quinazolinedione derivatives (QADs and QADDs, respectively) as second-generation antagonists. Initial in silico docking studies suggested that these compounds would bind to DAD2, the petunia strigolactone receptor, with higher affinity than the first-generation compounds. However, only one of the QADs/QADDs tested in in vitro assays acted as a competitive antagonist of strigolactone receptors, with reduced affinity and potency compared with its N -phenylanthranilic acid "parent". X-ray crystal structure analysis revealed that the binding mode of the active QADD inside DAD2's cavity was not that predicted in silico , highlighting a novel inhibition mechanism for strigolactone receptors. Despite a ~10-fold...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research