Arene-selective peptide and protein derivatization

Chelate complexes of Ru(II) (12a,b) featuring an eta(5)-C-5,eta(1)-N-C5H4(C H2)(n)NH2 ligand (n = 2, 3) have been synthesized as arene-selective protei n modification reagents. The new chelates produce eta(6)-arene complexes fr om a wide variety of arenes, from 1,4-di-t-butylbenzene to phenylalanine-co ntaining peptides and proteins. In methanol or nitromethane at room tempera ture (r.t.), kinetic products are formed by coordination of the Ru center t o Nand S-donors (primary amines, histidine, methionine, cystine), but warmi ng to 60 degrees C leads to migration of the Ru center to a phenylalanine r ing, with the formation of eta(6)-arene complexes as robust thermodynamic p roducts. Notably, in water the complex 12a reacts at r.t. with the 27-resid ue protein secretin, which contains a phenylalanine residue, to give an eta (6)-arene complex, which can be purified by HPLC and analyzed by electrospr ay and MALDI-MS. (C) 1999 Elsevier Science S.A. All rights reserved.