37841-04-6

Upstream product

• 108-24-7 acetic anhydride 
• 368-16-1 3-methyl-L-histidine 

Downstream Products

• 368-16-1 3-methyl-L-histidine 

Relevant academic research and scientific papers

New regioselectivity in the cleavage of histidine-containing peptides by palladium(II) complexes studied by kinetic experiments and molecular dynamics simulations

Palladium(II) complexes promote hydrolytic cleavage of amide bonds in N- acetylhistidylglycine (AcHis-Gly), N-acetylhistidine (AcHis), and their derivatives methylated at the N-1 or N-3 atom of imidazole. Methylation controls coordination of imidazole to palladium(II) and allows stereochemical analysis of the reactions. The complex [PdCl4]2- regioselectively cleaves the amide bond involving the carboxylic group of histidine, the bond His- Gly; the rate constants of cleavage are virtually the same when the peptides coordinate to palladium(II) via the N-1 and the N-3 atom. The complex [Pd(H2O)4]2+ cleaves, at comparable rates, the amide bonds involving both the carboxylic (His-Gly) and the amino (AcHis) groups of histidine in the acetylated dipeptide. This unprecedented reactivity is examined by theoretical calculations in which molecular dynamics and solution of Poisson- Boltzmann equation are combined in a new way. When the Pd(H2O)32+ group is attached to the N-1 atom, both scissile bonds can be cleaved by internal delivery of aqua ligands. When the Pd(H2O)32+ group is attached to the N- 3 atom, both scissile bonds can be cleaved by internal delivery of aqua ligands and by external attack of water; in some conformers the two modes of cleavage may be combined in the reaction mechanism. In both N-1 and N-3 linkage isomers internal delivery seems to be assisted by weak hydrogen bonding. The rate constants for cleavage by [Pd(H2O)4]2+ are approximately 10 times greater than those for cleavage by [PdCl4]2-. This difference is explained semiquantitatively by consideration of the aquation equilibria involving [PdCl4]2-. This study shows that kinetics and regioselectivity of peptide cleavage may be controlled simply by choosing ligands in palladium(II) complexes. This is another step in our development of simple metal complexes as artificial metallopeptidases.

β-Hydroxydecanoyl Thioester Dehydrase. Complete Characterization ot the Fate of the "Suicide" Substrate 3-Decynoyl-NAC

β-Hydroxydecanoyl thioester dehydrase, the pivotal enzyme in the biosynthesis of unsaturated fatty acids under anaerobic conditions, catalyzes the interconversion of thioesters of (R)-3-hydroxydecanoic acid (1), (E)-2-decenoic acid (2), and (Z)-3-decenoic acid (3).Dehydrase is irreversibly inactivated by the N-acetylcysteamine thioester of 3-decynoic acid (3-decynoyl-NAC), via dehydrase-catalyzed conversion of the acetylenic thioester to 2,3-decadienoyl-NAC.This is the classic example of "suicide" or "mechanism-based" enzyme inactivation.NMR-based experiments have been carried out in order to define the mechanistic relationship between "normal" catalysis and suicide inactivation of dehydrase, by providing detailed structural information on the enzyme-bound inactivator moiety. 3-Decynoyl-NAC was synthesized and incubated with homogeneous dehydrase. (13)C NMR spectroscopy at 100.6 MHz showed that when 2,3-decadienoyl-NAC is attacked by the active-site histidine, the product is (3-imidazolyl-3-decenoyl)-NAC.This adduct is slowly isomerized to (3-imidazolyl-2-decenoyl)-NAC.One molecule of inactivator is bound per subunit of the dimeric enzyme.Model histidine-allene adducts have been made and characterized.Comparisons of NMR data reveal that the double-bond configuration of the decenoyl moiety of the enzyme-bound inactivator is E.Analysis of these findings strongly suggests that the histidine residue that is alkylated by 2,3-decadienoyl-NAC is the active-site base.The structure of the product formed by inactivation of dehydrase by 3-decynoyl-NAC and the mechanism of the inactivation are readily explained in terms of the mechanisms of the normal dehydrase-catalyzed reactions as well as the stereochemical relationships between enzyme and substrates in those normal reactions.