The 3D structure of thuricin CD, a two-component bacteriocin with cysteine sulfur to α-carbon cross-links

Thuricin CD is an antimicrobial factor that consists of two peptides, Trn-α and Trn-β, that exhibit synergistic activity against drug resistant strains of Clostridium difficile. Trn-α and Trn-β each possess three sulfur to α-carbon thioether bridges for which the stereochemistry is unknown. This report presents the three-dimensional solution structures of Trn-α and Trn-β. Structure calculations were performed for the eight possible stereoisomers of each peptide based on the same NMR data. The structure of the stereoisomer that best fit the experimental data was chosen as the representative structure for each peptide. It was determined that Trn-α has L-stereochemistry at Ser21 (α-R), L-stereochemistry at Thr25 (α-R), and D-stereochemistry at Thr28 (α-S) (an LLD isomer). Trn-β was also found to be the LLD isomer, with L-stereochemistry at Thr21 (α-R), L-stereochemistry at Ala25 (α-R), and D-stereochemistry at Tyr28 (α-S).     

The structure of some α, β-unsaturated sulfur compounds from dipole moment data

Summary Measurements have been made of the dipole moments of the following , -unsaturated organic sulfur compounds: vinylethylsulfide (1.38 D), vinylbutylsulfide (1.40 D), vinylphenylsulfide (1.27 D), vinylethylsulfoxide (3.80 D), vinylbutylsulfoxide (3.78 D), vinylphenylsulfoxide (3.83 D), divinylsulfone (4.41 D), vinylethylsulfone (4.43 D), vinylbutylsulfone (4.45 D), 1,2-diethylsulfonylethylene, cis-(2.69 D) and trans- (1.36 D)-isomers and 1,4-dibutylsulfonylbutadiene-1,3-cis-trans-(5.19 D), cis-cis-(4.11 D) and trans-trans-(4.19 D)-isomers. Some conclusions are drawn as to the structure of the compounds investigated.     

Reconstruction of the 3D coordinates of α-carbon atoms of proteins from a pair of stereographic figures

Summary In an attempt to promptly use the experimentally determined structures of proteins in modeling studies, we have developed the program ReconstC to generate the 3D coordinates of -carbon atoms from a pair of stereographic figures. Calculations of the 3D coordinates were performed by estimating the stereo parameters systematically. Geometrical features of C traces were used to evaluate the integrity of the calculated structure. The program was applied to four kinds of protein structures to examine the performance. It was found that the root-mean-square deviation of atomic positions between constructed and reference crystal structures ranged from 0.36 to 0.78 Å. The range represents a reasonable accuracy and its automatic feature suggests that our approach would be expedient for providing initial structures for protein modeling studies.     

Enantioselective electrophilic bond construction to the α-carbon of α-aminoacids

In this report, we describe three possibilities for aminoacid synthesis using an enantioselective electrophilic process. Thus, enantioselective carboxylation, alkylation and protonation of Schiff bases yield optically active aminoacids with e.e. up to 76%.     

Secondary structure analysis of peptides with relevance to iron–sulfur cluster nesting

Peptides coordinated to iron–sulfur clusters, referred to as maquettes, represent a synthetic strategy for constructing biomimetic models of iron–sulfur metalloproteins. These maquettes have been successfully employed as building blocks of engineered heme-containing proteins with electron-transfer functionality; however, they have yet to be explored in reactivity studies. The concept of iron–sulfur nesting in peptides is a leading hypothesis in Origins-of-Life research as a plausible path to bridge the discontinuity between prebiotic chemical transformations and extant enzyme catalysis. Based on past biomimetic and biochemical research, we put forward a mechanism of maquette reconstitution that guides our development of computational tools and methodologies. In this study, we examined a key feature of the first stage of maquette formation, which is the secondary structure of aqueous peptide models using molecular dynamics simulations based on the AMBER99SB empirical force field. We compared and contrasted S…S distances, [2Fe-2S] and [4Fe-4S] nests, and peptide conformations via Ramachandran plots for dissolved Cys and Gly amino acids, the CGGCGGC 7-mer, and the GGCGGGCGGCGGW 16-mer peptide. Analytical tools were developed for following the evolution of secondary structural features related to [Fe-S] cluster nesting along 100 ns trajectories. Simulations demonstrated the omnipresence of peptide nests for preformed [2Fe-2S] clusters; however, [4Fe-4S] cluster nests were observed only for the 16-mer peptide with lifetimes of a few nanoseconds. The origin of the [4Fe-4S] nest and its stability was linked to a “kinked-ribbon” peptide conformation. Our computational approach lays the foundation for transitioning into subsequent stages of maquette reconstitution, those being the formation of iron ion/iron–sulfur coordinated peptides. © 2018 Wiley Periodicals, Inc.     

Insertion of cyclopropanes between a carbonyl carbon and an α-carbon of carbonyl compounds with cyclopropylmagnesium carbenoids

The reaction of the lithium enolates of α-aryl carbonyl compounds with cyclopropylmagnesium carbenoids, derived from 1-chlorocyclopropyl p-tolyl sulfoxides with i-PrMgCl at low temperature, resulted in the formation of β-aryl carbonyl compounds bearing a cyclopropane ring at the α-position with one-carbon homologation in variable yields. The reaction was found to be highly stereospecific with respect to the stereochemistry of the cyclopropylmagnesium carbenoids. Mechanism and origin of the stereospecificity of the reaction are also discussed. This is the first example for the insertion of cyclopropanes in between a carbonyl carbon and an α-carbon of carbonyl compounds.     

The rate of intramolecular end-to-end photodimerisation of α,ω-dianthrylpolystyrene in solution

To study the effect of molecular weight on the rate of the intramacromolecular end-to-end reaction of a flexible polymer, the intramolecular photodimerisation of α,ω-dianthrylpolystyrene has been carried out by successive illumination with a 337 nm pulsed nitrogen laser of a dilute solution of butanone at 30°C. The extent of dimerisation against the number of pulses (measured fluorometrically) was converted, based on several assumptions, to the apparent diffusion-controlled rate constants for polymer cyclisation. The rate constants for polymer cyclisation decrease in proportion to DP^−0·3 for the range of DP = 110–2600. The implications of this result in the chain dynamics of polymers are briefly discussed.     

Halonium-initiated C-O bond formation via umpolung of α-carbon to the carbonyl: efficient access to 5-amino-3(2H)-furanones

Highly efficient C-O bond formation has been developed via carboxylic acid catalyzed reaction of 1-acetylcyclopropanecarboxamides with N-halosuccinimide (NXS), which provides strategically novel and atom-economic access to biologically important 5-amino-3(2H)-furanones. The mechanism of halonium-initiated tandem oxa-cyclization and ring opening of cyclopropane was proposed. A variety of nucleophiles were found to open the cyclopropane.     

The synthesis,structure, and some reactions of sterically hindred α-silylisoxazoles

4-(4,5-Dihydro-4,4-dimethyl-2-isoxazolyl)-3-phenyl-5-silylmethylisozazole and 3-phenyl-5-silylmethyl-4-isoxazole-t-carboxamide derivatives were synthesized in synthetically useful yields from the corresponding oxazolyl-isoxazole or t-carboxamide by metalation of the isoxazole systems at the C(5) alkyl group followed by electrophilic quenching with either t-butylchlorodiphenylsilane or t-butylchlorodimethylsilane. The silylisoxazole systems were metalated at the C(5) position, producing the corresponding α-silyl carbanion, which upon quenching with MeOD produced C(5) deuterium incorporation. The reaction of silyloxazolylisoxazoles with titanium tetrachloride caused the oxazoline ring to open forming chloro-substituted carboxamide. The X-ray structure of a silyloxazolylisoxazole was obtained and indicates an “s-trans” ring juncture with respect to the heterocyclic rings.     

Synthesis of stable oxazolidine nitroxyl radicals with methoxy groups at the α-carbon atoms to the radical site

The condensation of -hydroxyaminoalcohols with aldehydes and acetone gave 3-hydroxyoxazolidines and tautomeric N-(2-hydroxyethyl)--arylnitrones, whose oxidation by PbO₂ in methanol leads to stable oxazolidine nitroxyl radicals with methoxy groups at C² and C⁴.Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 4, pp. 966–973, April, 1992.     

The susceptibility of α-helical secondary structure to steric strain: Coarse-grained simulation of dendronized polypeptides

The propensity of a peptide chain for adopting helical secondary structure can be modulated not only through the solvation properties of its side chains but also through their size and shape. Here we examine a coarse-grained model for dendronized polypeptides that focuses on the susceptibility of α-helical structure to the steric strain exerted by hydrophilic pendant groups. Undecorated molecules exhibit a pronounced transition from random coil to helix upon cooling [J. P. Kemp and J. Z. Y. Chen, Biomacromolecules 2, 389 (2001)]. As gauged by specific heat and by order parameters characterizing helicity at several length scales, this transition is quite robust to the introduction of first- and second-generation dendron side chains. More highly branched side chains, however, reduce the entropy of compact states so severely that helical ordering is undetectable over the entire temperature range accessible to our importance sampling methods. Consistent with experimental observations for side chains comparable to those of our model in volume-excluding size and shape, we find the backbone of these third-generation molecules to assume a distended rodlike state that is both stiff and achiral.     

The condensation reaction of methylphosphonic acid with α,ω-diethoxydimethylsiloxanes

Russian Chemical Bulletin -     

The Reaction of α,α-Dichlorobenzyltrimethylsilane with Aldehydes and Ketones

The reaction of α,α-dichlorobenzyltrimethylsilane with carbonyl compounds in the presence of fluoride ion fails to give reasonable yields of the α,α-dichlorobenzyl adducts except when carried out in the presence of zinc iodide and in HMPA as solvent. Under these conditions moderate yields of the adducts can be obtained with cyclohexanone, cyclohexenone, benzaldhyde and trans cinnamaldehyde. These reactions were compared with those of α,α-dichlorobenzyllithium.