SYNTHESIS, STRUCTURE, AND PROPERTIES OF MESER(1)-TENTOXIN, A NEW CYCLIC TETRAPEPTIDE WHICH INTERACTS SPECIFICALLY WITH CHLOROPLAST F1 H-ATPASE DIFFERENTIATION OF INHIBITORY AND STIMULATING EFFECTS()

A new tentoxin analogue, in which the L-methyl alanine residue is subs tituted by L-methylserine, has been prepared following the synthetic p athway recently described for the synthesis of tentoxin [Cavelier, F., & Verducci, J. (1995) Tetrahedron Lett. 36, 4425-4428]. Using two-dim ensional homonuclear proton nuclear magnetic resonance and structural analysis, we observed that MeSer(1)-tentoxin, like tentoxin, adopts se veral conformations in aqueous solution and presents self-aggregative properties. This analogue was found to be conformationally similar to the natural toxin. It showed the same efficiency as tentoxin in inhibi tion of ATPase activity of the isolated chloroplast F-1 proton ATPase (CF1) as well as in inhibition of the ATP synthase activity of the mem brane-bound enzyme (CF0CF1) in thylakoids and proteoliposomes. At conc entrations above 10 mu M, MeSer(1)-tentoxin did not reactivate CF1 to a high extent, contrary to tentoxin. It appeared, however, to bind in the same way, since the reactivating effect of tentoxin was inhibited by MeSer(1)-tentoxin. These results show that it is possible, using te ntoxin analogues, to separate inhibitory and activating effects on the chloroplast ATPase, despite the limited chemical difference between t he two toxins.