422284-53-5Relevant articles and documents
Chemical approaches to protein engineering 20: The transformation of coded amino acid tyrosine to pro-templates having metal uptake potential in peptide/protein segments
Ranganathan,Tamilarasu
, p. 1081 - 1103 (2007/10/03)
From vantage of inorganic chemistry, the inability of any of the coded amino acid side chains to carry metal ions should appear as a grave omission in the genetic code, particularly since, metallo-enzymes play a pivotal role in diverse facets of life processes. The ready transformation of the coded amino acid tyrosine to metal uptake systems forms the core of the present work. 3-Acetyl-tyrosine [Tyr(3-Ac)]- readily derived from tyrosine is amenable to normal protocols in peptide synthesis and offers ideal ligand dispositions to craft protemplates. This aspect has been illustrated by three broad strategies. The reaction of Tyr(3-Ac) with AEH, the mono Schiff base of acetylacetone and ethylenediamine (EDA), yields the protemplates II [TYr(3-Ac)-AEH] which can also be conveniently assembled, in situ, from acetylacetone, EDA and Tyr(3-Ac). Tripeptide, where Tyr(3-Ac) is flanked by Ala and Ser has been prepared and protemplate formation demonstrated in a peptide environment. Thus, either by normal peptide synthesis or by insertion of peptides containing Tyr(3-Ac), active sites for metal uptake can be constructed, thereby, in principle, obviating the need for 50-70 residues normally required. Protemplates for metal uptake can be readily crafted by cross linking of Tyr(3-Ac) with EDA. This has also been illustrated with Ala-Tyr(3-Ac)-Ser-OMe. Thus, peptides where Tyr(3-Ac) is placed at appropriate locations, with EDA, can provide conformationally restrained metal uptake systems. Conversely, the oxime of Tyr(3-Ac) as well as the Schiff bases with β-ethanolamine and Gly-OMe can bring together proximate residues by metal complexation. This aspect has been experimentally realized. The protemplates from Tyr(3-Ac) [Schiff bases with AEH / EDA / β-ethanolamine / Gly-OMe / and oximes] readily take up Cu(II), Co(II), and Ni(II) to form stable, well defined templates. The EPR spectra of the Cu(II) templates are that for typical square planar complexes, although in few sterically crowded examples rhombohedral distortion was seen. The observed A and g parameters compared favorably with that reported for metalloproteins, with particular closeness to laccase. Cyclic voltammetric studies were complicated by incursion of ligand oxidation, although in two cases clear E° values of 340 mV and 305 mV were obtained, which lie in the range reported for metallo-proteins. The Ni(II) templates exhibited the expected 1H NMR profile; in one example, coordination with two water molecules was seen. The Co(II) templates exhibited typical d-d transition at ～600 nm in the visible spectrum.
