[Tentoxin: structure-activity relationship. Application to the study of its action on chloroplast ATP-synthase]

A mini review of the properties of the natural phytotoxin, tentoxin, is proposed. In particular, the biological activities of tentoxin on the chloroplast F0F1 proton ATPase, which realizes the synthesis of ATP at the expense of an electrochemical gradient of protons, are discussed. In this respect, structure-activity relationships of tentoxin have been re-examined in the light of the recent developments obtained by two-dimensional proton nuclear magnetic resonance (81). The conformations of the cyclic tetrapeptide [cyclo-(L-MeAla1-L-Leu2-MePhe[(Z) delta]3-Gly4)] have been studied in aqueous solution at various temperatures. Contrary to what was observed in early studies in chloroform, tentoxin was proved to exhibit multiple exchanging conformations in water. Four conformations with different proportions (51, 37, 8 and 4%) were found. Models were derived from nuclear magnetic resonance parameters and restrained molecular dynamics simulations. They confirmed that the four conformers exhibited the cis-trans-cis-trans configuration of the amide bond sequence. The conversion from one form to another is accomplished by a conformational peptide flip consisting of a 180 degrees rotation of a non-methylated peptide bond. In addition, important aggregation phenomena were observed. These effects have also been evidenced in chloroform, and compared to results derived from experiments carried out in the presence of DPC micelles. The tentoxin molecule was found self-associated in solution in a micellar-like organization. On the basis of these observations, we propose to design new analogues, with the intention of elucidating the mode of action of tentoxin in plants on the molecular level, especially under the aspect of its interaction with the chloroplast ATPase.