Molecular Recognition of Methionine-Terminated Peptides by Cucurbit[8]uril.

This Article describes the molecular recognition of peptides containing an N-terminal methionine (Met) by the synthetic receptor cucurbit[8]uril (Q8) in aqueous solution and with submicromolar affinity. Prior work established that Q8 binds with high affinity to peptides containing aromatic amino acids, either by simultaneous binding of two aromatic residues, one from each of two different peptides, or by simultaneous binding of an aromatic residue and its immediate neighbor on the same peptide. The additional binding interface of two neighboring residues suggested the possibility of targeting nonaromatic peptides, which have thus far bound only weakly to synthetic receptors.

Engineering oxidative stability in human hemoglobin based on the Hb providence (βK82D) mutation and genetic cross-linking.

Previous work suggested that hemoglobin (Hb) tetramer formation slows autoxidation and hemin loss and that the naturally occurring mutant, Hb Providence (HbProv; βK82D), is much more resistant to degradation by HO We have examined systematically the effects of genetic cross-linking of Hb tetramers with and without the HbProv mutation on autoxidation, hemin loss, and reactions with HO, using native HbA and various wild-type recombinant Hbs as controls. Genetically cross-linked Hb Presbyterian (βN108K) was also examined as an example of a low oxygen affinity tetramer. Our conclusions are: (a) at low concentrations, all the cross-linked tetramers show smaller rates of autoxidation and hemin loss than HbA, which can dissociate into much less stable dimers and (b) the HbProv βK82D mutation confers more resistance to degradation by HO, by markedly inhibiting oxidation of the β93 cysteine side chain, particularly in cross-linked tetramers and even in the presence of the destabilizing Hb Presbyterian mutation.

Electrochromic poly(acetylene)s with switchable visible/near-IR absorption characteristics.

Ferrocene is incorporated into a poly(acetylene) derivative via the postpolymerization amidation of a polymer precursor bearing pentafluorophenyl ester-leaving groups with aminoferrocene. While the neutral polymer exhibits a strong absorbance at 553 nm due to its conjugated backbone, oxidation of the ferrocene moieties with silver tetrafluoroborate causes the material to absorb in the near-IR (λ max ≈ 1215 nm). Subsequent reduction of the oxidized polymer with decamethylferrocene restores the initial absorbance profile, demonstrating that the material features switchable visible/near-IR absorption characteristics.

Synthesis and study of olefin metathesis catalysts supported by redox-switchable diaminocarbene[3]ferrocenophanes.

A redox-switchable ligand, N,N'-dimethyldiaminocarbene[3]ferrocenophane (5), was synthesized and incorporated into a series of Ir- and Ru-based complexes. Electrochemical and spectroscopic analyses of (5)Ir(CO)2Cl (15) revealed that 5 displayed a Tolman electronic parameter value of 2050 cm(-1) in the neutral state and 2061 cm(-1) upon oxidation. Moreover, inspection of X-ray crystallography data recorded for (5)Ir(cis,cis-1,5-cyclooctadiene)Cl (13) revealed that 5 was sterically less bulky (%V(Bur) = 28.

Redox-switchable ring-closing metathesis: catalyst design, synthesis, and study.

High yielding syntheses of 1-(ferrocenylmethyl)-3-mesitylimidazolium iodide (1) and 1-(ferrocenylmethyl)-3-mesitylimidazol-2-ylidene (2) were developed. Complexation of 2 to [{Ir(cod)Cl}2] (cod=cis,cis-1,5-cyclooctadiene) or [Ru(PCy3)Cl2(=CH-o-O-iPrC6H4)] (Cy=cyclohexyl) afforded 3 ([Ir(2)(cod)Cl]) and 5 ([Ru(2)Cl2(=CH-o-O-iPrC6H4)]), respectively. Complex 4 ([Ir(2)(CO)2Cl]) was obtained by bubbling carbon monoxide through a solution of 3 in CH2Cl2.

Development of recombinant hemoglobin-based oxygen carriers.

Significance: The worldwide blood shortage has generated a significant demand for alternatives to whole blood and packed red blood cells for use in transfusion therapy. One such alternative involves the use of acellular recombinant hemoglobin (Hb) as an oxygen carrier.

Recent Advances: Large amounts of recombinant human Hb can be expressed and purified from transgenic Escherichia coli.

Enhancing the peroxidatic activity of KatG by deletion mutagenesis.

Catalase-peroxidase (KatG) enzymes use a peroxidase active site to facilitate robust catalase activity, an ability all other members of its superfamily lack. KatG's have a Met-Tyr-Trp covalent adduct that is essential for catalatic but not peroxidatic turnover. The tyrosine (Y226 in E.

Blind prediction of host-guest binding affinities: a new SAMPL3 challenge.

The computational prediction of protein-ligand binding affinities is of central interest in early-stage drug-discovery, and there is a widely recognized need for improved methods. Low molecular weight receptors and their ligands--i.e.

Mesohaem substitution reveals how haem electronic properties can influence the kinetic and catalytic parameters of neuronal NO synthase.

NOSs (NO synthases, EC 1.14.13.

1,1'-Bis(N-benzimidazolylidene)ferrocene: synthesis and study of a novel ditopic ligand and its transition metal complexes.

Diiridum complexes containing 1,1'-bis(N-benzimidazolylidene)ferrocene, a novel ditopic ligand comprised of two N-heterocyclic carbenes (NHCs) linked directly via their N-substituents to each cyclopentadienyl ring of a ferrocene moiety, were synthesized. Crystallographic analyses of these C(2)-symmetric bimetallic complexes revealed the benzimidazolylidene moieties were intramolecularly stacked in nearly opposing orientations, effectively forming Janus-type bis(NHC) structures in the solid state. Using a variety of electrochemical techniques, the oxidation potentials of the ferrocenyl groups in these complexes were found to depend on the auxillary ligands coordinated to the Ir centers (i.

System for the expression of recombinant hemoproteins in Escherichia coli.

Expression of recombinant hemoproteins in Escherichia coli is often limited because a vast majority of the protein produced lacks the heme necessary for function. This is compounded by the fact that standard laboratory strains of E. coli have a limited capacity to withdraw heme from the extracellular environment.

Properties of a novel periplasmic catalase-peroxidase from Escherichia coli O157:H7.

A subset of catalase-peroxidases are distinguished by their periplasmic location and their expression by pathogens. Kinetic and spectral properties have not been reported for any of these enzymes. We report the cloning, expression, isolation, and characterization of KatP, a periplasmic catalase-peroxidase from Escherichia coli O157:H7.

Regulation of rat liver hydroxymethylglutaryl coenzyme A reductase by a new class of noncompetitive inhibitors. Effects of dichloroacetate and related carboxylic acids on enzyme activity.

Dichloroacetate (DCA) markedly reduces circulating cholesterol levels in animals and in patients with combined hyperlipoproteinemia or homozygous familial hypercholesterolemia (FH). To investigate the mechanism of its cholesterol-lowering action, we studied the effects of DCA and its hepatic metabolites, glyoxylate and oxalate, on the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) obtained from livers of healthy, reverse light-cycled rats. Oral administration of DCA for 4 d decreased HMG CoA reductase activity 46% at a dose of 50 mg/kg per d, and 82% at a dose of 100 mg/kg per d.

Dietary carbohydrate decreases 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol synthesis in rat liver.

Diets high in carbohydrate and low in fat led to a decrease in the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in livers of healthy, reverse light-cycled rats. The effect on reductase was due both to a decline in expressed enzyme activity and to a decrease in total number of enzyme molecules. Inhibition of reductase activity was paralleled by a fall in hepatic cholesterolgenesis and by an increase in triglyceride formation.

Stimulation of rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity by o,p'-DDD.

To investigate the mechanism by which o'p'-DDD (2,2-bis [2-chlorphenyl-4-chlorophenyl]-1,1-dichloroethane; Mitotane) produces hypercholesterolemia in man, we studied the effect of the drug on hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity in reverse light-cycled rats. o,p'-DDD markedly stimulated reductase activity in vivo and in vitro in a dose-dependent manner. This effect was not associated with demonstrable adrenocortical toxicity or changes in plasma corticosterone concentrations.