The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform

B. V. Subba Reddy - One of the best experts on this subject based on the ideXlab platform.

N. Siva Senkar Reddy - One of the best experts on this subject based on the ideXlab platform.

Yadav Jhillu Singh - One of the best experts on this subject based on the ideXlab platform.

Gunter Fischer - One of the best experts on this subject based on the ideXlab platform.

  • The hsp70 chaperone DnaK is a Secondary Amide peptide bond cis-trans isomerase.
    Nature Structural & Molecular Biology, 2002
    Co-Authors: Cordelia Schiene-fischer, Judith Maria Habazettl, Gunter Fischer
    Abstract:

    Peptidyl prolyl cis-trans isomerases can enzymatically assist protein folding, but these enzymes exclusively target the peptide bond preceding proline residues. Here we report the identification of the Hsp70 chaperone DnaK as the first member of a novel enzyme class of Secondary Amide peptide bond cis-trans isomerases (APIases). APIases selectively accelerate the cis-trans isomerization of nonprolyl peptide bonds. Results from independent experiments support the APIase activity of DnaK: (i) exchange crosspeaks between the cis-trans conformers appear in 2D 1H NMR exchange spectra of oligopeptides (ii) the rate constants for the cis-trans isomerization of various dipeptides increase and (iii) refolding of the RNase T1 P39A variant is catalyzed. The APIase activity shows both regio and stereo selectivity and is stimulated two-fold in the presence of the complete DnaK/GrpE/DnaJ/ATP refolding system. Moreover, known DnaK-binding oligopeptides simultaneously affect the APIase activity of DnaK and the refolding yield of denatured firefly luciferase in the presence of DnaK/GrpE/DnaJ/ATP. These results suggest a new role for the chaperone as a regioselective catalyst for bond rotation in polypeptides.

  • direct measurement indicates a slow cis trans isomerization at the Secondary Amide peptide bond of glycylglycine
    Journal of the American Chemical Society, 2001
    Co-Authors: Cordelia Schienefischer, Gunter Fischer
    Abstract:

    Spectral differences between the cis and the trans isomer of a Secondary Amide peptide bond were used to follow the time course of the cis/trans isomerization of Gly-Gly, Gly-Ala, Ala-Gly, and Ala-Ala dipeptides in the UV/vis region at 220 nm. Isomerization rates and Eyring activation energies were calculated from pH- and LiCl-mediated solvent jump experiments. Rate constants were found to be in a narrow range of 0.29 to 0.64 s(-)(1) for the zwitterionic dipeptides at 25 degrees C. The isomerization rate is about 2-fold higher for the monoionic forms of Gly-Gly. The zwitterionic Gly-Gly has an activation enthalpy DeltaH() of 71.6 +/- 4.9 kJ mol(-)(1) that is in the range of the rotational barriers of aromatic side chain dipeptides that have been measured by (1)H NMR magnetization transfer experiments. Late stages of protein backbone rearrangements often involve crossing the energy barrier for rotational isomerization of imidic peptide bonds. Our findings are consistent with the idea that a wide range of Secondary Amide peptide bonds are also able to induce slow rate-limiting steps in protein restructuring.

  • Direct Measurement Indicates a Slow Cis/Trans Isomerization at the Secondary Amide Peptide Bond of Glycylglycine
    Journal of the American Chemical Society, 2001
    Co-Authors: Cordelia Schiene-fischer, Gunter Fischer
    Abstract:

    Spectral differences between the cis and the trans isomer of a Secondary Amide peptide bond were used to follow the time course of the cis/trans isomerization of Gly-Gly, Gly-Ala, Ala-Gly, and Ala-Ala dipeptides in the UV/vis region at 220 nm. Isomerization rates and Eyring activation energies were calculated from pH- and LiCl-mediated solvent jump experiments. Rate constants were found to be in a narrow range of 0.29 to 0.64 s(-)(1) for the zwitterionic dipeptides at 25 degrees C. The isomerization rate is about 2-fold higher for the monoionic forms of Gly-Gly. The zwitterionic Gly-Gly has an activation enthalpy DeltaH() of 71.6 +/- 4.9 kJ mol(-)(1) that is in the range of the rotational barriers of aromatic side chain dipeptides that have been measured by (1)H NMR magnetization transfer experiments. Late stages of protein backbone rearrangements often involve crossing the energy barrier for rotational isomerization of imidic peptide bonds. Our findings are consistent with the idea that a wide range of Secondary Amide peptide bonds are also able to induce slow rate-limiting steps in protein restructuring.

  • Barriers to Rotation of Secondary Amide Peptide Bonds
    Journal of the American Chemical Society, 1998
    Co-Authors: Gerd Scherer, Michael L. Kramer, Mike Schutkowski, And Ulf Reimer, Gunter Fischer
    Abstract:

    We present results on the identification and molecular characterization of conformers with Secondary cis Amide peptide bonds for a number of oligopeptides containing tyrosine and phenylalanine in a...

Neil K. Garg - One of the best experts on this subject based on the ideXlab platform.

  • nickel catalyzed transamidation of aliphatic Amide derivatives
    Chemical Science, 2017
    Co-Authors: Jacob E Dander, Emma L Baker, Neil K. Garg
    Abstract:

    Transamidation, or the conversion of one Amide to another, is a long-standing challenge in organic synthesis. Although notable progress has been made in the transamidation of primary Amides, the transamidation of Secondary Amides has remained underdeveloped, especially when considering aliphatic substrates. Herein, we report a two-step approach to achieve the transamidation of Secondary aliphatic Amides, which relies on non-precious metal catalysis. The method involves initial Boc-functionalization of Secondary Amide substrates to weaken the Amide C–N bond. Subsequent treatment with a nickel catalyst, in the presence of an appropriate amine coupling partner, then delivers the net transamidated products. The transformation proceeds in synthetically useful yields across a range of substrates. A series of competition experiments delineate selectivity patterns that should influence future synthetic design. Moreover, the transamidation of Boc-activated Secondary Amide derivatives bearing epimerizable stereocenters underscores the mildness and synthetic utility of this methodology. This study provides the most general solution to the classic problem of Secondary Amide transamidation reported to date.

  • a two step approach to achieve Secondary Amide transamidation enabled by nickel catalysis
    Nature Communications, 2016
    Co-Authors: Emma L Baker, Michael M Yamano, Sarah M Anthony, Yujing Zhou, Neil K. Garg
    Abstract:

    A long-standing challenge in synthetic chemistry is the development of the transamidation reaction. This process, which involves the conversion of one Amide to another, is typically plagued by unfavourable kinetic and thermodynamic factors. Although some advances have been made with regard to the transamidation of primary Amide substrates, Secondary Amide transamidation has remained elusive. Here we present a simple two-step approach that allows for the elusive overall transformation to take place using non-precious metal catalysis. The methodology proceeds under exceptionally mild reaction conditions and is tolerant of amino-acid-derived nucleophiles. In addition to overcoming the classic problem of Secondary Amide transamidation, our studies expand the growing repertoire of new transformations mediated by base metal catalysis.