Penicillin biosynthesis: Retention of configuration at c-3 of valine during its incorporation into the arnstein tripeptide

[3-³H]-valine was efficiently synthesised from sodium α-ketoisovalerate. With a β-lactam negative mutant of C. acremonium, l-[1-¹⁴C-3-³H]-valine and dl-[1-¹⁴C-3-³H]-valine were independently incorporated into the Arnstein tripeptide dimer, i.e. Bis-δ-(l-α-aminodipyl)-l-cystinyl-bis-d-valine, with full retention of trieium at C-3 of the d-valine residue. This result strongly suggested retention of configuration at C-3 of valine when the tripeptide was biosynthesised, and further limited the number of possible mechanisms for the biosynthesis of penicillins.     

Ribosomal synthesis of unnatural peptides

Combinatorial libraries of non-biological polymers and drug-like peptides could in principle be synthesized from unnatural amino acids by exploiting the broad substrate specificity of the ribosome. The ribosomal synthesis of such libraries would allow rare functional molecules to be identified using technologies developed for the in vitro selection of peptides and proteins. Here, we use a reconstituted E. coli translation system to simultaneously re-assign 35 of the 61 sense codons to 12 unnatural amino acid analogues. This reprogrammed genetic code was used to direct the synthesis of a single peptide containing 10 different unnatural amino acids. This system is compatible with mRNA-display, enabling the synthesis of unnatural peptide libraries of 10(14) unique members for the in vitro selection of functional unnatural molecules. We also show that the chemical space sampled by these libraries can be expanded using mutant aminoacyl-tRNA synthetases for the incorporation of additional unnatural amino acids or by the specific posttranslational chemical derivitization of reactive groups with small molecules. This system represents a first step toward a platform for the synthesis by enzymatic tRNA aminoacylation and ribosomal translation of cyclic peptides comprised of unnatural amino acids that are similar to the nonribosomal peptides.     

Reactions of metal ions with dithizone in molten naphthalene

A comparative study has been made of the reactions of metal ions with dithizone in the two media, chloroform and molten naphthalene. The absorption spectra of several metal dithizonates, prepared in molten naphthalene, were recorded and were found to be the same as those of the dithizonates obtained by extraction of metal ions from aqueous solution with chloroform dithizone.     

Synthesis of marine sponge alkaloid hachijodine B and a comment on the structure of ikimine B and on the absolute configuration of niphatesine D

The syntheses of the proposed structures of hachijodine B 1, ikimine B 2 and niphatesine D 3 from S-citronellol are described. Our results suggest that the gross structures of hachijodine B and niphatesine D are correct, but that ikimine B was incorrectly assigned. We have also established that the previous absolute stereochemical assignment for niphatesine D is unreliable.     

SIMULTANEOUS MEASUREMENT OF ACTION SPECTRA FOR PHOTOREACTIONS I AND II OF PHOTOSYNTHESIS

Abstract— We have devised a method of obtaining simultaneous action spectra for photoreactions I and II by analysis of direct and indirect effects involved in enhancement. The method requires previous determination of the neutral wavelength which gives maximum quantum yield by virtue of equal fractions of open reaction centers ( p and q ) for each photoreaction. A sufficient intensity of the neutral wavelength is used as a constant background. Upon addition of a weak modulated measuring light of intensity I_m and wavelength λ _m two amperometric signals are obtained for rate of oxygen evolution. A modulated signal (AC¯) isolates the direct effect of I_m and gives action of photoreaction II as AC/ I_m . An increment in total rate (ΔDC) also includes an indirect effect of I_m in perturbing reaction center conditions ( p and q ). From analysis of interaction of the two photoreactions, action for photoreaction I can be estimated as (2 ΔDC-AC)/ I_m . The method is applicable to whole cells, properly scales the two action spectra to each other, and removes contribution of the State 1-State 2 phenomena. Action spectra were obtained for Chlorella.     

Chromatographic and mass spectral studies on isobaric and isomeric substances related to 3,4-methylenedioxymethamphetamine

A series of isobaric and isomeric molecules related to 3,4methylenedioxymethamphetamine (3,4-MDMA) are prepared and evaluated as potential mass spectral equivalents to this controlled substance. These compounds have the potential to produce a mass spectrum equivalent to 3,4-MDMA, thus making mass spectrometry a nonconclusive method for confirming the identity of any one of the substances. The various isomeric forms of the methoxymethylphenethylamines and the methoxymethcathinones have mass spectra essentially equivalent to 3,4-MDMA, but the ethoxy substituted phenethylamines show a unique fragment at m/z 107. Gas chromatographic separation on nonpolar stationary phases successfully resolved these compounds from 3,4-MDMA, however only a limited set of side chain regioisomers and ring substitution patterns are evaluated in this initial study.     

JACOB: An enterprise framework for computational chemistry

Here, we present just a collection of beans (JACOB): an integrated batch‐based framework designed for the rapid development of computational chemistry applications. The framework expedites developer productivity by handling the generic infrastructure tier, and can be easily extended by user‐specific scientific code. Paradigms from enterprise software engineering were rigorously applied to create a scalable, testable, secure, and robust framework. A centralized web application is used to configure and control the operation of the framework. The application‐programming interface provides a set of generic tools for processing large‐scale noninteractive jobs (e.g., systematic studies), or for coordinating systems integration (e.g., complex workflows). The code for the JACOB framework is open sourced and is available at: www.wallerlab.org/jacob . © 2013 Wiley Periodicals, Inc.     

E.S.R. and D.S.C. investigations of phase transitions in polymorphic 4-n-alkoxybenzylidene-4′-n-alkylanilines

Abstract

It is shown that the McMillan parameter M = T _SAN/T _N1 (where T _SAN and T _NI are respectively the temperatures of the smectic A to nematic (SAN) and the nematic to isotropic (NI) phase transitions) is useful in analysing the crossover between second and first order behaviour of the S_NN transition in the nO.m homologous liquid crystal series (the 4-n-alkoxybenzylidene-4′-n-alkylanilines). Using a phase diagram of orientational ordering versus M for this series, as obtained in this work (from E.S.R. and D.S.C), a symmetric tricritical point with mean field exponent β₂ = 1 is demonstrated. In a preliminary study of E.S.R. linewidth parameters B and C of nitroxide spin probes dissolved in members of the nO.m series exhibiting a first order S_AN transition, critical-type divergences are observed near this transition. In the case where M is closer to 0.959 (the value at the tricritical point), these divergences appear similar to those previously observed in related nO.m members with a second order S_AN transition; however, they are considerably enhanced for an M value closer to unity (i.e. more removed from the tricritical point). This indicates the importance of coupling between orientational and positional order parameters in the observed critical-type divergences.