Effects of tail-like substituents on the binding of competitive inhibitorsto the Q(B) site of photosystem II

The Q(B) quinone-binding site of photosystem II is an important target for herbicides, Two major classes of herbicides are based on s-triazine and phe nylurea moieties, A small library of triazine and phenylurea compounds has been synthesized which have tail-like substituents in order to test the eff ects of charge, hydrophobicity and size of the tail on binding properties. It is found that a tail can be attached to one of the alkylamino groups of triazine-type herbicides or to the para position of phenylurea-type herbici des without loss of binding, provided that the tail is hydrophobic, This in dicates that the herbicides must be oriented in the Q(B) site such that the se positions point toward the natural isoprenyl tail-binding pocket that ex tends out of the Q(B) site. In turn, the requirement that the tail must ext end out of the Q(B) site constrains the size of the other herbicide substit uents in the pocket. This is in agreement with the presumed orientation and fit of ligands in the Q(B) site, When longer hydrophobic tails are used, t he binding penalty that occurs upon adding a charged substituent at the dis tal end is reduced. This allows the use of a series of tail substituents po ssessing a distal charge as an approximate molecular ruler to measure the d istance from the Q(B) site to the aqueous phase, Even a 10-carbon alkyl cha in still shows a 4-fold effect from the presence or absence of a distal cha rge, Such a chain does not appear to be long enough to extend from the bulk aqueous phase to the Q(B) site because binding is completely lost when a l arge hydrophilic domain (PEG(4000)) is attached to the distal end. Longer t ails are effective only if they are sufficiently hydrophobic, An effort was made to use tailed herbicides for affinity binding of photosystem II, It w as found that hydrophobic linkers promote nonspecific binding, but careful choice of solvent conditions, such as the use of excess nonionic detergent well above its critical micelle concentration, might obviate this problem d uring affinity-binding applications. Copyright (C) 2001 John Wiley & Sons, Ltd.