Binding phenylureas

Certain substituted urea compounds, such as phenylurea or thidiazuron. Fig. (1), are very effective in the replacement of adenine-based cytokinins in promoting callus growth and other bioassays [27,28]. Molecular modeling revealed that the energetically optimal conformation of active urea derivatives have similar geometry as the isoprenoid side chain, so they can bind to the active sites of cytokinin metabolic enzymes and/or activate cytokinin receptors [29]. Thus, these compounds are likely to enhance their cytokinin effect by simultaneous activation of the receptor and inhibition of some of the cytokinin deactivating enzymes [11,30]. 

Photosynthetic herbicides fall into three main groups phenylureas, triazines, diazines and phenols, depending on their chemical structure and binding properties. Although both classes of herbicides replace the Qp acceptor on the D1 protein, they interact with different amino acid residues on Dl. ... 

Bowyer J, Hilton M, Whitelegge J et al. Molecular modelling studies on the binding of phenylurea inhibitors to the D1 protein of photosystem II. Z Naturforsch 1990 45c 379-387. 

Whereas inhibition of chloroplast electron transport has been correlated with binding to a protein(s), the sites and mechanisms through which herbicides interfere with mitochondrial and chloroplast mediated phosphorylations remain to be identified. When lipophilic herbicides partition into the lipid phases of membranes, they could perturb lipid-lipid, lipid-protein, and protein-protein interactions that are required for membrane functions such as electron transport, ATP formation, and active transport. Evidence for general membrane perturbations caused by chlorpropham, 2,6-dinitroanilines, perfluidone, and certain phenylureas have been reported previously (8-11). 

The competitive binding experiments of Tischer and Strotmann (4) suggest that the phenylureas, biscarbamates, triazines, tria-zinones, and pyridazinones inhibit electron transport by interaction with the same component of PS II. Action at this site seemed to account for the phytotoxicity of pyrazon [5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone]. In addition to action at this site, compounds with molecular substitutions onto the structure of pyrazon (Figure 1) also interfere with the formation of chloroplast membrane lipids, namely the chlorophylls, carotenoids, and glycerolipids. 

In 1999 Masabni and Zandstra reported on a mutant of Portulaca oleracea with a resistance pattern to PS II inhibitors that was different to most triazine resistant weeds [28], This mutant was resistant to the phenylureas linuron and diuron, but also cross-resistant to atrazine and other triazines. Sequencing of the D1 protein revealed that in the resistant biotype the serine 264 was replaced by threonine and not by glycine. This was the first report on a serine 264 to threonine mutation on a whole plant level. It was proposed that the serine-to-threonine mutation modified the conformation of the herbicide binding niche at the D1 protein in a way, which resulted in reduced binding of phenylureas and triazines as well. 

Use of 3(3-azido-4 chlorophenyl)-1,1-dimethylurea (azidomonuron), a photoaffinity labelling analogue of the herbicidal phenylurea 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), has revealed Tyr 237 and Tyr 254 of D1 to be close to the herbicide binding site (1). An interesting property of DCMU is its ability, under certain conditions, to displace a bicarbonate ion which normally binds to PS2 in the region of the non-heme ferrous atom situated between and Qg. 

Pertinently substituted -triazines are known to inhibit PS II electron flow in chloroplasts and are herbicidal [20], and also phenylurea and carbamate herbicides are known to act at the same site as that of 5 -triazines [17]. In other words, they are bioisosters to each other with respect to the binding to the action site, or the bioisosterism between them is fairly high, irrespective of the apparently different structures. Moreover, phenylureas are known to have cytokinin activity [4,6]. Thus, the carbamates are expected to behave bioisosterically to phenylureas or 5 -triazines with respect to the interaction with the cytokinion receptor. 

Zanoni reported on the assembly of AuNPs on calixarene-based SAMs [85]. A silicon surface (Si) was functionalized with a calix[6]arene derivative bearing three undecenyl chains on the lower rim and three phenylurea moieties on the upper rim (Ce). The so-produced SAMs form stable complexes with a redox-active molecule that consists of a 4,4 -bypiridinium unit linked by a dodecyl chain to another pyridinium ring (A). This surface showed binding towards AuNPs functionalized with a calix[4]arene derivative (C4) (Fig. 37.15). The presence of the di-topic guests allows for the reversible and hierarchical assembly of the AuNPs on the Si surface. Moreover, the nanoparticles were demonstrated to be electrochemically removed from the Si/Ce/A surface. 

Another azidopyridine derivative, l-(2-azido-6-ehloropyrid-4-yl)-3-phenylurea was used as photoaffinity labeling reagent for cytokinin-binding proteins [112], In the absenee of the 6-ehloro substituent, the tetrazole form was the only existing tautomer. The corresponding compound did not exhibit cytokinin activity and was not photolysable. 

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