The Experts below are selected from a list of 141 Experts worldwide ranked by ideXlab platform
Arieh Warshel - One of the best experts on this subject based on the ideXlab platform.
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on catalytic preorganization in oxyanion holes highlighting the problems with the gas phase modeling of oxyanion holes and illustrating the need for complete Enzyme Models
Journal of Organic Chemistry, 2010Co-Authors: Shina Caroline Lynn Kamerlin, Arieh WarshelAbstract:Oxyanion holes play a major role in catalyzing enzymatic reactions, yet the corresponding energetics is frequently misunderstood. The main problem may be associated with the nontrivial nature of the electrostatic preorganization effect, without following the relevant formulation. That is, although the energetics of oxyanion holes have been fully quantified in early studies (which include both the enzymatic and reference solution reactions), the findings of these studies are sometimes overlooked, and, in some cases, it is assumed that gas-phase calculations with a fixed model of an oxyanion hole are sufficient for assessing the corresponding effect in the protein. Herein, we present a systematic analysis of this issue, clarifying the problems associated with modeling oxyanions by means of two fixed water molecules (or related constructs). We then re-emphasize the point that the effect of the oxyanion hole is mainly due to the fact that the relevant dipoles are already set in an orientation that stabilizes ...
Shina Caroline Lynn Kamerlin - One of the best experts on this subject based on the ideXlab platform.
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on catalytic preorganization in oxyanion holes highlighting the problems with the gas phase modeling of oxyanion holes and illustrating the need for complete Enzyme Models
Journal of Organic Chemistry, 2010Co-Authors: Shina Caroline Lynn Kamerlin, Arieh WarshelAbstract:Oxyanion holes play a major role in catalyzing enzymatic reactions, yet the corresponding energetics is frequently misunderstood. The main problem may be associated with the nontrivial nature of the electrostatic preorganization effect, without following the relevant formulation. That is, although the energetics of oxyanion holes have been fully quantified in early studies (which include both the enzymatic and reference solution reactions), the findings of these studies are sometimes overlooked, and, in some cases, it is assumed that gas-phase calculations with a fixed model of an oxyanion hole are sufficient for assessing the corresponding effect in the protein. Herein, we present a systematic analysis of this issue, clarifying the problems associated with modeling oxyanions by means of two fixed water molecules (or related constructs). We then re-emphasize the point that the effect of the oxyanion hole is mainly due to the fact that the relevant dipoles are already set in an orientation that stabilizes ...
Florian Hollfelder - One of the best experts on this subject based on the ideXlab platform.
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from Enzyme Models to model Enzymes
2009Co-Authors: Anthony J Kirby, Florian HollfelderAbstract:Introduction Evaluation Classification by model system Classification by reaction Problems Glossary Index
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polyethylene imine derivatives synzymes accelerate phosphate transfer in the absence of metal
Journal of the American Chemical Society, 2007Co-Authors: Frederic Avenier, Josiel B Domingos, Liisa D Van Vliet, Florian HollfelderAbstract:The efficient integration of binding, catalysis, and multiple turnovers remains a challenge in building Enzyme Models. We report that systematic derivatization of polyethylene imine (PEI) with alkyl (C2-C12), benzyl, and guanidinium groups gives rise to catalysts (‘synzymes') with rate accelerations (kcat/kuncat) of up to 104 for the intramolecular transesterification of 2-hydroxypropyl-p-nitrophenyl phosphate, HPNP, in the absence of metal. The synzymes exhibit saturation kinetics (KM ≈ 250 μM, kcat ≈ 0.5 min-1) and up to 2340 turnovers per polymer molecule. Catalysis can be specifically and competitively inhibited by anionic and hydrophobic small molecules. The efficacy of catalysis is determined by the PEI derivatization pattern. The derivatization reagents exert a synergistic effect, i.e., their combinations increase catalysis by more than the sum of each single modification. The pH−rate profile for kcat/KM is bell shaped with a maximum at pH 7.85 and can be explained as a combination of two effects t...
Wolfgang Tremel - One of the best experts on this subject based on the ideXlab platform.
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Functional Enzyme Mimics for Oxidative Halogenation Reactions that Combat Biofilm Formation
Advanced Materials, 2018Co-Authors: Karoline Herget, Hajo Frerichs, Felix Pfitzner, Muhammad Nawaz Tahir, Wolfgang TremelAbstract:Transition-metal oxide nanoparticles and molecular coordination compounds are highlighted as functional mimics of halogenating Enzymes. These Enzymes are involved in halometabolite biosynthesis. Their activity is based upon the formation of hypohalous acids from halides and hydrogen peroxide or oxygen, which form bioactive secondary metabolites of microbial origin with strong antibacterial and antifungal activities in follow-up reactions. Therefore, Enzyme mimics and halogenating Enzymes may be valuable tools to combat biofilm formation. Here, halogenating Enzyme Models are briefly described, Enzyme mimics are classified according to their catalytic functions, and current knowledge about the settlement chemistry and adhesion of fouling organisms is summarized. Enzyme mimics with the highest potential are showcased. They may find application in antifouling coatings, indoor and outdoor paints, polymer membranes for water desalination, or in aquacultures, but also on surfaces for food packaging, door handles, hand rails, push buttons, keyboards, and other elements made of plastic where biofilms are present. The use of natural compounds, formed in situ with nontoxic and abundant metal oxide Enzyme mimics, represents a novel and efficient "green" strategy to emulate and utilize a natural defense system for preventing bacterial colonization and biofilm growth.
Jean-louis Reymond - One of the best experts on this subject based on the ideXlab platform.
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expanding the topological space of bioactive peptides
Chimia, 2013Co-Authors: Jean-louis Reymond, Tamis DarbreAbstract:Naturally occurring peptides and proteins consist almost exclusively of linear or cyclic polypeptide chains. Our group explores the chemical space of peptides by redesigning their topology through the introduction of branching points in the peptide chain. Branched peptides are generally resistant to proteolysis and display remarkable biological properties by multivalency effects (peptide dendrimers) and conformational rigidity (polycyclic peptides). We review our recent progress in peptide dendrimers as Enzyme Models, biofilm inhibitors, antimicrobials, DNA transfection and cell-penetrating agents, and in the synthesis and characterization of bicyclic peptides as new scaffolds for drug design.
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peptide and glycopeptide dendrimer apple trees as Enzyme Models and for biomedical applications
Organic and Biomolecular Chemistry, 2012Co-Authors: Jean-louis Reymond, Tamis DarbreAbstract:Solid phase peptide synthesis (SPPS) provides peptides with a dendritic topology when diamino acids are introduced in the sequences. Peptide dendrimers with one to three amino acids between branches can be prepared with up to 38 amino acids (MW ∼ 5,000 Da). Larger peptide dendrimers (MW ∼ 30,000) were obtained by a multivalent chloroacetyl cysteine (ClAc) ligation. Structural studies of peptide dendrimers by CD, FT-IR, NMR and molecular dynamics reveal molten globule states containing up to 50% of α-helix. Esterase and aldolase peptide dendrimers displaying dendritic effects and Enzyme kinetics (kcat/kuncat ∼ 105) were designed or discovered by screening large combinatorial libraries. Strong ligands for Pseudomonas aeruginosa lectins LecA and LecB able to inhibit biofilm formation were obtained with glycopeptide dendrimers. Efficient ligands for cobalamin, cytotoxic colchicine conjugates and antimicrobial peptide dendrimers were also developed showing the versatility of dendritic peptides. Complementing the multivalency, the amino acid composition of the dendrimers strongly influenced the catalytic or biological activity obtained demonstrating the importance of the “apple tree” configuration for protein-like function in peptide dendrimers.
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Peptide dendrimer Enzyme Models for ester hydrolysis and aldolization prepared by convergent thioether ligation
Organic & biomolecular chemistry, 2011Co-Authors: Nicolas A. Uhlich, Tamis Darbre, Jean-louis ReymondAbstract:Peptide dendrimers with multiple histidines or N-terminal prolines efficiently catalyze ester hydrolysis or aldol reactions in aqueous medium. Part of the catalytic proficiency of these dendritic Enzyme Models stems from multivalency effects observed in G2, G3 and G4 dendrimers displaying multiple catalytic groups in their branches. To study multivalency in higher generation systems, G4, G5 and G6 peptide dendrimers were prepared by a convergent assembly. Thus, peptide dendrimers bearing four or eight chloroacetyl groups at their N-termini underwent multiple thioether ligation with G2 and G3 peptide dendrimers with a cysteine residue at their focal point, to give G4, G5 and G6 dendrimers containing up to 341 amino acids, including multiple histidines or N-terminal prolines. While the efficiency of the esterase catalysts was comparable to that of their lower generation analogs, a remarkable reactivity increase was observed in G5 and G6 aldolase dendrimers.