Electrostatic effects on
(di)terpene synthase product outcome
Effect of specifically located hydroxyl group in counter-acting effect of pyrophosphate anion co-product in steering carbocation migration towards itself (e.g. by further cyclization, as shown).
Cytochromes P450 as useful biocatalysts: addressing the limitations
Factors limiting the exploitation of cytochrome P450s and significant steps which have been taken towards addressing these limitations are discussed.
Probing the stereoselectivity of P-glycoprotein—synthesis, biological activity and
ligand docking studies of a set of enantiopure benzopyrano[3,4-b][1,4]oxazines
Enantiomerically pure benzopyrano[3,4-b][1,4]oxazines show significant differences in their inhibitory potency of P-glycoprotein. Docking studies provide first insights into potential binding sites for these compounds.
A new dehydrogenase from Clostridium acetobutylicum for asymmetric synthesis: dynamic reductive kinetic resolution entry into the Taxotère side chain
Asymmetric carbonyl reduction using a new Clostridium acetobutylicum ADH provides access to diverse value-added chiral building blocks using biorenewable redox equivalents.
Incorporation of chlorinated analogues of aliphatic
amino acids during cell-free protein synthesis
Analogues of Val and Leu having a chloro substituent in place of a methyl group are efficiently incorporated into protein.
Competing SN2 and E2 reaction pathways for hexachlorocyclohexane degradation in the gas phase, solution and enzymes
Quantum chemistry calculations reveal that the isomer specificity of enzymes that break down hexachlorocyclohexane is constrained by the intrinsic substrate reactivity.
Ribonuclease S redux
Modern methods ease the use and enhance the versatility of an historical protein-fragment complementation system.
Screening of a minimal enriched P450 BM3 mutant library for
hydroxylation of cyclic and acyclic alkanes
Several single and double mutants from a minimal cytochrome P450 BM3 library were found to effectively oxidize cyclic and acyclic alkanes. For example, the F87A/A328V mutant hydroxylates cyclododecane to cyclododecanol.
Biocompatible functionalisation of starch
A combination of enzymatic synthesis and click chemistry is employed for the production of starch derivatives under mild, aqueous reaction conditions.
A fast and sensitive assay for measuring the activity and enantioselectivity of transaminases
A fast and sensitive method for screening transaminase activity and enantioselectivity, using D- and L-amino acid oxidases, allows new amine substrates to be rapidly identified.
Micelle to fibre biocatalytic supramolecular transformation of an aromatic
A mechanistic insight into a phosphatase-driven supramolecular transformation whereby a peptide amphiphile switches from micellar structure to a chiral nanofibre morphology.
Probing the proteasome cavity in three steps: bio-orthogonal photo-reactive suicide substrates
Tri-functional activity-based proteasome probes are used for a three-step chemical proteomics approach, in which proteasomal catalytic sites are covalently and irreversibly modified, followed by photocrosslinking of these to flanking subunits and Staudinger–Bertozzi ligation for visualization and identification of the resulting conjugates.
Photochemical cleavage of leader
A photolabile linker is described for light-mediated removal of leader peptides involved in biosynthesis of posttranslationally modified peptide natural products.
labeling of polypeptides using protein farnesyltransferase via rapid oxime ligation
An aldehyde-containing substrate for protein farnesyltransferase was shown to be enzymatically incorporated into a protein. The protein was subsequently immobilized onto aminooxy-functionalized agarose beads or labeled with a fluorophore. This method provides an alternative to the commonly employed Cu(I)-catalyzed click reaction.
Towards preparative-scale, biocatalytic
Reaction strategies for employing two complementary alkene reductase enzymes in laboratory-scale conversions have been developed.
Increasing the stability of an
enzyme toward hostile organic solvents by directed evolution based on iterative saturation mutagenesis using the B-FIT method
Mutants of Bacillus subtilis lipase evolved for enhanced thermostability also show increased stability in organic solvents such as acetonitrile (ACN).
Michael addition of water and in situ oxidation
MhyADH catalyses the Michael addition of water and also the subsequent oxidation to a diketone. In the absence of an oxidation reagent the reaction stops after the Michael addition.
Tandem driven dynamic self-inhibition of acetylcholinesterase
A concept of tandem driven dynamic enzyme self-inhibition is demonstrated for acetylcholinesterase through the action of dynamic stealth inhibitors using reversible transthiolesterification.
Profiling small molecule
inhibitors against helix– receptor interactions: the Bcl-2 family inhibitor BH3I-1 potently inhibits p53/hDM2
We validate a practical methodology for the rapid profiling of small molecule inhibitors of protein–protein interactions. We find that a well known BH3 family inhibitor can potently inhibit the p53/hDM2 interaction.
Cyclen-hybrid compound captures
copper to protect INS-1 cells from islet amyloid polypeptide cytotoxicity by inhibiting and lysing effects
I1–Cu(II) inhibits hIAPP cytotoxicity by interfering with aggregation and cleavage.
Simultaneous iridium catalysed
oxidation and enzymatic reduction employing orthogonal reagents
Employing orthogonal reaction conditions an iridium catalysed oxidative hydrogen transfer was successfully coupled concurrently to an asymmetric enzyme catalysed reduction.
Structural and biochemical basis for the firm chemo- and regioselectivity of the
nitro-forming N-oxygenase AurF
Variants of the N-oxygenase AurF from Streptomyces thioluteus selectively transform guanidyl- and amidinyl-substituted anilines into the corresponding nitro compounds. Site-directed mutagenesis and structural data provide new insights into regioselective N-oxygenation.
Fluorinase mediated chemoenzymatic synthesis of [18F]-fluoroacetate
A novel preparation of sodium [18F]-fluoroacetate is described by a fluorinase catalysed reaction of S-adenosyl-L-methionine 1 with no carrier added [18F]-fluoride and then the [18F]-2 product is oxidized to [18F]-fluoroacetate by a Kuhn–Roth oxidative degradation.
inhibitors targeting the CCR5- binding site on the human immunodeficiency virus type-1 gp120 glycoprotein complexed to CD4
The display of two sulfotyrosine residues in the α-helical fold of CCR5 can be mimicked in a β-hairpin peptidomimetic.
dimerization programmed by hybridization to study multimeric ligand– receptor interactions
Peptidic ligands (16mer macrocycles) were dimerized with different geometries programmed by hybridization to recapitulate the interaction of TRAIL.
Structure–activity relationships of the
phosphonate antibiotic dehydrophos
A series of analogs of dehydrophos were prepared and tested for their antimicrobial activity.
A fluopol-ABPP HTS assay to identify
A fluopol-ABPP HTS assay identifies streptonigrin as a potent and selective PAD4 inactivator.
Interaction of PqqE and PqqD in the
pyrroloquinoline quinone ( PQQ) biosynthetic pathway links PqqD to the radical SAM superfamily
Data are presented that show PqqD interacting with PqqE.
Structural insights into substrate specificity and
solvent tolerance in alcohol dehydrogenase ADH-‘A’ from Rhodococcus ruber DSM 44541
The first structures of the widely-used alcohol dehydrogenase ADH-‘A’ provide new avenues for the structure-guided engineering of this useful enzyme.
isopropyl amine: equilibrium displacement with yeast alcohol dehydrogenase coupled to in situ cofactor regeneration
The unfavourable equilibrium in a transamination with isopropylamine is displaced in an enzymatic cascade reaction using alcohol dehydrogenase in situ.
Chemoenzymatic asymmetric total synthesis of
(S)-Rivastigmine using ω-transaminases
Asymmetric total synthesis of (S)-Rivastigmine was achieved via stereoselective biocatalytic transamination of acetophenone derivatives.
Rational creation of mutant
enzyme showing remarkable enhancement of catalytic activity and enantioselectivity toward poor substrates
Catalytic activity and enantioselectivity of lipase toward poor substrates bearing bulky substituents on both sides have been dramatically improved by rational design; the E value was increased from 5 (wild-type enzyme) to >200 (I287F/I290A double mutant) with an acceleration of the reaction rate.
Inverting the enantioselectivity of P450pyr monooxygenase by directed evolution
The first example of directed evolution of a novel P450pyr monooxygenase with inverted enantioselectivity has been demonstrated.
Silver catalyzed cascade synthesis of alkaloid ring systems: concise total synthesis of fascaplysin, homofascaplysin C and analogues
A silver catalyzed and microwave assisted one-pot cascade synthesis provides efficient access to diverse alkaloid-inspired scaffold classes, and a concise and efficient total synthesis of homofascaplysin C and fascaplysin.
amyloid formation: an approach for studying peptide aggregation
A strategy has been demonstrated that utilizes a phosphatase as a natural tool for the triggering and control of amyloid formation in a coiled coil peptide model under conditions that closely approximate a physiological environment.
amino acid that mimics phosphotyrosine
By replacing the phosphate group in pTyr with an isoxazole carboxylic acid, a novel unnatural amino acid has been successfully synthesized. Subsequently, its incorporation into a known PPI (protein–protein interaction) inhibitor of STAT3 protein (ISS 610) generated I2 which showed reasonable anti-STAT3 activity in both fluorescence polarization and cell-proliferation experiments.
Solid phase total synthesis of the
3-amino-6-hydroxy-2-piperidone (Ahp) cyclodepsipeptide and protease inhibitor Symplocamide A
The Ahp cyclodepsipeptide Symplocamide A was synthesized on solid phase, using an unsaturated amino acid as a key building block for the formation of the central Ahp moiety.
Computational design of orthogonal
Rosetta design software was employed to remodel the substrate specificity of Drosophila melanogaster 2′-deoxyribonucleoside kinase for efficient phosphorylation of the nucleoside analog prodrug 3′-deoxythymidine.
O-Glycoligases, a new category of
glycoside bond-forming mutant glycosidases, catalyse facile syntheses of isoprimeverosides
Near quantitative yields of alpha-xyloside products were obtained by coupling alpha-xylosyl fluoride with sugar acceptors using the acid/base mutant D482A of the GH31 alpha-xylosidase Yic-I
Comparing dendritic with linear esterase
peptides by screening SPOT arrays for catalysis
Direct fluorescence screening of a peptide library on a SPOT array identified oligohistidines as potent esterase peptides for the hydrolysis of acetoxypyrene trisulfonates.
Characterization of xenobiotic reductase A (XenA): study of
active site residues, substrate spectrum and stability
Characterization on xenobiotic reductase A and its mutants for enzyme functionality and stability.
Total chemical synthesis of human proinsulin
The protein enantiomers D- and L-proinsulin have been prepared by total synthesis using native chemical ligation.
Total chemical synthesis and X-ray structure of kaliotoxin by racemic
The first X-ray structure of kaliotoxin, enabled by ‘one pot’ chemical ligation of synthetic peptides and racemic protein crystallography.
probes for imaging endosymbiotic bacteria within toxic dinoflagellates
We report a technique to visualize toxic dinoflagellates and suggest a preventative tool to warn of an impending danger and ensure the safe delivery of shellfish to the consumer market.
Phage display selection of miniprotein binders of the Estrogen Receptor
Phage display selection of disulfide stabilized miniproteins identified Estrogen Receptor binders displaying an LXXLL motif on a short peptide helix.
Engineering of an enantioselective
tyrosine aminomutase by mutation of a single active site residue in phenylalanine aminomutase
An engineered tyrosine aminomutase with high enantioselectivity was constructed by homology-modelling based mutagenesis of the active site of phenylalanine aminomutase.
About this collection
This web-based themed issue showcases high quality papers in the field of chemical biology, specifically research that deals with enzymes and proteins. The collated, invited, and peer-reviewed ChemComm articles highlight cutting edge contributions by international leaders in the field.
The guest editors of this web themed issue are Professors Nicholas Turner, Wilfred van der Donk and Herbert Waldmann. They are delighted by the overwhelming response that the letter of invitation produced and they express their sincere thanks to the authors. The articles received and published cover a diverse range of contemporary topics in chemical biology including biosynthesis, biocatalysis, structure/function studies, drug design and proteins as sensors.
Articles in this web themed issue will be added to the list below as soon as possible, after they are published. Please return to this page frequently to see this collection grow.