Non-protein amino acids in peptide design

An overview of the use of non-protein amino acids in the design of conformationally well-defined peptides, based on work from the author’s laboratory, is discussed. The crystal structures of several designed oligopeptides illustrate the useα-aminoisobutyric acid (Aib) in the construction of helices, D-amino acids in the design of helix termination segments and^DPro-Xxx segments for nucleating ofβ-hairpin structures.β- andγ-amino acid residues have been used to expand the range of designed polypeptide structures. Dedicated to Professor C N R Rao on his 70th birthday     

Electron transfer induced dissociations of 2- and 4-alkyl cyclohexadienones

Several 2- and 4-alkylcyclohexadienones were prepared and shown to accept electrons to produce ketyl radical anions that dissociated rapidly at room temperature to release carbon-centered radicals and an aromatic phenoxide type anion. In the PET process with benzyl-substituted cyclohexadienones, initiated with triethylamine, the benzyl radicals dimerised or abstracted an H-atom from solvent. In electrochemical reductions, and in reductions with alkali metals in liquid ammonia, the benzyl radicals were further reduced to anions.     

Microwave-accelerated conjugate addition of aldehydes to α,β-unsaturated ketones

Aldehydes undergo smooth conjugate addition to α,β-unsaturated ketones in the presence of 5-(2-hydroxyethyl)-1,3-thiazolium halides and DBU adsorbed onto the surface of basic alumina under microwave irradiation and solvent-free conditions to afford 1,4-diketones in enhanced yields and reduced reaction times compared to conventional methods.     

Addition of Bromotrichloromethane and Tetrachloromethane to cis-Cyclooctene,Cyclohexene, and Norbornadiene in the Presence of Palladium(II) Complexes

Addition of bromotrichloromethane and tetrachloromethane to alkenes in the presence of palladium(II) complexes begins with single-electron transfer from the palladium atom to polyhalomethane molecule, followed by fragmentation of the radical anion thus formed and generation of trichloromethyl radical. Halogen transfer to a carbon-centered radical arising from addition of trichloromethyl radical at the double bond occurs both from the polyhalomethane molecule and from halide palladium complex.     

Synthesis and Structure of Mixed Phosphonium-iodonium Ylide

A mixed phosphonium-iodonium ylide, phenyliodoniumethoxycarbonylmethylenetriphenylphosphorane borofluoride, was synthesized. Its structure was established by means of X-ray diffraction analysis. Temperature dependence of ¹H, ¹³C, and ³¹P spectra of the ylide synthesized was investigated. A dynamic equilibrium between Z and E-isomers was observed.     

The evolution of a truncated gaussian probability density through time—modelling animal liveweights after selection

The form of the probability density derived from the evolution in time of a previously truncated frequency distribution of animal Liveweights is of interest in animal husbandry. Truncated frequency distributions arise when the heavier animals are sold for slaughter and the lighter animals retained. The demands of modern quality assurance schemes require that, given information on animal growth, the farmer is able to estimate the number of animals that would meet the specifications at some time in the future after truncation. Assuming that animal growth can be described by a linear stochastic differential equation, we derive an explicit expression for the probability density of animal Liveweights at any time after the truncation of an initial Gaussian density. It is shown that this probability density converges rapidly to a Gaussian density, so that after about 20 days of typical growth rates for lambs, the resulting density is practically indistinguishable from Gaussian.     

Three-dimensional structure of Saccharomyces cerevisiae inorganic pyrophosphatase complexed with cobalt and phosphate ions

Crystals of Saccharomyces cerevisiae inorganic pyrophosphatase suitable for X-ray diffraction study were grown by cocrystallization of the enzyme with cobalt chloride and imidodiphosphate. Saccharomyces cerevisiae is a metal-dependent enzyme which catalyzes hydrolysis of inorganic pyrophosphate to orthophosphate. The three-dimensional structure of this enzyme was solved by the molecular-replacement method and refined at 1.8 Å resolution to an R factor of 19.5%. Cobalt and phosphate ions were revealed in the active centers of both identical subunits (A and B) of the pyrophosphatase molecule. In subunit B, a water molecule was found between two cobalt ions. It is believed that this water molecule acts as an attacking nucleophile in the enzymatic cleavage of the pyrophosphate bond. It was demonstrated that cobalt ions and a phosphate group occupy only part of the potential binding sites (two chemically identical and crystallographically independent subunits have different binding sites). The arrangement of ligands and the structure of the nucleophile-binding site are discussed in relation to the mechanism of action of the enzyme and the nature of the metal activator.