scholarly journals Magnetization Lifetimes Prediction and Measurements Using Long-Lived Spin States in Endogenous Molecules

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5495
Author(s):  
F. Teleanu ◽  
C. Tuță ◽  
A. Cucoanes ◽  
S. Vasilca ◽  
P. R. Vasos
Keyword(s):  
Amino Acids ◽  
Chemical Shifts ◽  
Spin Dynamics ◽  
A Priori ◽  
Biologically Relevant ◽  
Spin Order ◽  
Biologically Relevant Molecules ◽  
Radiation Treatments ◽  
Experimental Values

Nuclear magnetization storage in biologically-relevant molecules opens new possibilities for the investigation of metabolic pathways, provided the lifetimes of magnetization are sufficiently long. Dissolution-dynamic nuclear polarization-based spin-order enhancement, sustained by long-lived states can measure the ratios between concentrations of endogenous molecules on a cellular pathway. These ratios can be used as meters of enzyme function. Biological states featuring intracellular amino-acid concentrations that are depleted or replenished in the course of in-cell or in-vivo tests of drugs or radiation treatments can be revealed. Progressing from already-established long-lived states, we investigated related spin order in the case of amino acids and other metabolites featuring networks of coupled spins counting up to eight nuclei. We detail a new integrated theoretical approach between quantum chemistry simulations, chemical shifts, J-couplings information from databanks, and spin dynamics calculations to deduce a priori magnetization lifetimes in biomarkers. The lifetimes of long-lived states for several amino acids were also measured experimentally in order to ascertain the approach. Experimental values were in fair agreement with the computed ones and prior data in the literature.

scholarly journals Enantioselective organocatalysis in the synthesis of biologically relevant compounds

2016 ◽  
Author(s):  
Lukasz Albrecht
Keyword(s):  
Organic Chemistry ◽  
Amino Acids ◽  
Organic Molecules ◽  
Asymmetric Induction ◽  
Chiral Catalyst ◽  
Biologically Relevant ◽  
Enantioselective Reactions ◽  
Asymmetric Organocatalysis ◽  
Biologically Relevant Molecules ◽  
Operational Simplicity

The development of methods for the preparation of biologically relevant compounds in an enantiomerically enriched form constitutes one of the most significant tasks in the contemporary organic chemistry. In particular, enantioselective reactions where prochiral substrates are converted into enantiomerically enriched products in the presence of chiral catalyst are of great importance. Recently, asymmetric organocatalysis, where simple organic molecules are used as catalysts of various enantiodifferentiating reactions, has become a highly useful synthetic tool enabling for the efficient asymmetric induction based on diverse activation modes. Herein, we report our studies on organocatalytic, enantioselective strategies for the synthesis of biologically relevant molecules such as: quaternary α-amino acids and their isoelectronic analogs α-aminophosphonates, benzo[1,5]oxazocines, α-methylidene-δ-lactones, α-alkylidene-ketones, furfural derivatives, and benzothiophenes. The devised approaches utilize readily available chiral organocatalysts to control stereo-chemical reaction outcomes. Operational simplicity, efficiency and high enantio- and diastereoselectivities are the main benefits of the developed strategies.

scholarly journals A structure-based deep learning framework for protein engineering

2019 ◽  
Author(s):  
Raghav Shroff ◽  
Austin W. Cole ◽  
Barrett R. Morrow ◽  
Daniel J. Diaz ◽  
Isaac Donnell ◽  
...  
Keyword(s):  
Neural Network ◽  
Amino Acids ◽  
Deep Learning ◽  
Protein Engineering ◽  
Convolutional Neural Network ◽  
State Of The Art ◽  
A Priori ◽  
Novel Proteins ◽  
Learning Framework

AbstractWhile deep learning methods exist to guide protein optimization, examples of novel proteins generated with these techniques require a priori mutational data. Here we report a 3D convolutional neural network that associates amino acids with neighboring chemical microenvironments at state-of-the-art accuracy. This algorithm enables identification of novel gain-of-function mutations, and subsequent experiments confirm substantive phenotypic improvements in stability-associated phenotypes in vivo across three diverse proteins.

Effect of Biologically-Relevant Molecules on the Physico-Chemical Properties of Amorphous Magnesium–Calcium Phosphate Nanoparticles

2021 ◽  
Vol 21 (5) ◽  
pp. 2872-2878
Author(s):  
Rita Gelli ◽  
Serena Salvestrini ◽  
Francesca Ridi
Keyword(s):  
Calcium Phosphate ◽  
Chemical Properties ◽  
Inorganic Particles ◽  
Biologically Relevant ◽  
Distal Small Intestine ◽  
Physico Chemical ◽  
Calcium Phosphate Nanoparticles ◽  
Biologically Relevant Molecules ◽  
The Stability

The recently-discovered endogenous formation of amorphous magnesium–calcium phosphate nanoparticles (AMCPs) in human distal small intestine occurs in a complex environment, which is rich in biologically-relevant molecules and macromolecules that can shape the properties and the stability of these inorganic particles. In this work, we selected as case studies four diverse molecules, which have different properties and are representative of intestinal luminal components, namely butyric acid, lactose, gluten and peptidoglycan. We prepared AMCPs in the presence of these four additives and we investigated their effect on the features of the particles in terms of morphology, porosity, chemical nature and incorporation/adsorption. The combined use of electron microscopy, infrared spectroscopy and thermal analysis showed that while the morphology and microstructure of the particles do not depend on the type of additive present during the synthesis, AMCPs are able to incorporate a significant amount of peptidoglycan, similarly to the process in which they are involved in vivo.

scholarly journals The Use of Chromatin Immunoprecipitation to Define PpsR Binding Activity in Rhodobacter sphaeroides 2.4.1

2008 ◽  
Vol 190 (20) ◽  
pp. 6817-6828 ◽  
Author(s):  
Patrice Bruscella ◽  
Jesus M. Eraso ◽  
Jung Hyeob Roh ◽  
Samuel Kaplan
Keyword(s):  
Rhodobacter Sphaeroides ◽  
Chromatin Immunoprecipitation ◽  
Regulatory Networks ◽  
Binding Activity ◽  
Photosynthetic Membrane ◽  
New Members ◽  
Membrane Function ◽  
Biologically Relevant ◽  
Biologically Relevant Molecules

ABSTRACT The expression of genes involved in photosystem development in Rhodobacter sphaeroides is dependent upon three major regulatory networks: FnrL, the PrrBA (RegBA) two-component system, and the transcriptional repressor/antirepressor PpsR/AppA. Of the three regulators, PpsR appears to have the narrowest range of physiological effects, which are limited to effects on the structural and pigment biosynthetic activities involved in photosynthetic membrane function. Although a PrrA− mutant is unable to grow under photosynthetic conditions, when a ppsR mutation was present, photosynthetic growth occurred. An examination of the double mutant under anaerobic-dark-dimethyl sulfoxide conditions using microarray analysis revealed the existence of an “extended” PpsR regulon and new physiological roles. To characterize the PpsR regulon and to better ascertain the significance of degeneracy within the PpsR binding sequence in vivo, we adapted the chromatin immunoprecipitation technique to R. sphaeroides. We demonstrated that in vivo there was direct and significant binding by PpsR to newly identified genes involved in microaerobic respiration and periplasmic stress resistance, as well as to photosynthesis genes. The new members of the PpsR regulon are located outside the photosynthesis gene cluster and have degenerate PpsR binding sequences. The possible interaction under physiologic conditions with degenerate binding sequences in the presence of other biologically relevant molecules is discussed with respect to its importance in physiological processes and to the existence of complex phenotypes associated with regulatory mutants. This study further defines the DNA structure necessary for PpsR binding in situ.

scholarly journals Enantioselective organocatalysis in the synthesis of biologically relevant compounds

2016 ◽  
Author(s):  
Lukasz Albrecht
Keyword(s):  
Organic Chemistry ◽  
Amino Acids ◽  
Organic Molecules ◽  
Asymmetric Induction ◽  
Chiral Catalyst ◽  
Biologically Relevant ◽  
Enantioselective Reactions ◽  
Asymmetric Organocatalysis ◽  
Biologically Relevant Molecules ◽  
Operational Simplicity

The development of methods for the preparation of biologically relevant compounds in an enantiomerically enriched form constitutes one of the most significant tasks in the contemporary organic chemistry. In particular, enantioselective reactions where prochiral substrates are converted into enantiomerically enriched products in the presence of chiral catalyst are of great importance. Recently, asymmetric organocatalysis, where simple organic molecules are used as catalysts of various enantiodifferentiating reactions, has become a highly useful synthetic tool enabling for the efficient asymmetric induction based on diverse activation modes. Herein, we report our studies on organocatalytic, enantioselective strategies for the synthesis of biologically relevant molecules such as: quaternary α-amino acids and their isoelectronic analogs α-aminophosphonates, benzo[1,5]oxazocines, α-methylidene-δ-lactones, α-alkylidene-ketones, furfural derivatives, and benzothiophenes. The devised approaches utilize readily available chiral organocatalysts to control stereo-chemical reaction outcomes. Operational simplicity, efficiency and high enantio- and diastereoselectivities are the main benefits of the developed strategies.

scholarly journals Formation of nucleobases in a Miller–Urey reducing atmosphere

2017 ◽  
Vol 114 (17) ◽  
pp. 4306-4311 ◽  
Author(s):  
Martin Ferus ◽  
Fabio Pietrucci ◽  
Antonino Marco Saitta ◽  
Antonín Knížek ◽  
Petr Kubelík ◽  
...  
Keyword(s):  
Amino Acids ◽  
Electric Discharge ◽  
State Of The Art ◽  
Gas Mixture ◽  
Biologically Relevant ◽  
Reducing Atmosphere ◽  
Biologically Relevant Molecules ◽  
Impact Simulations ◽  
Primordial Earth ◽  
Theoretical Results

The Miller–Urey experiments pioneered modern research on the molecular origins of life, but their actual relevance in this field was later questioned because the gas mixture used in their research is considered too reducing with respect to the most accepted hypotheses for the conditions on primordial Earth. In particular, the production of only amino acids has been taken as evidence of the limited relevance of the results. Here, we report an experimental work, combined with state-of-the-art computational methods, in which both electric discharge and laser-driven plasma impact simulations were carried out in a reducing atmosphere containing NH3 + CO. We show that RNA nucleobases are synthesized in these experiments, strongly supporting the possibility of the emergence of biologically relevant molecules in a reducing atmosphere. The reconstructed synthetic pathways indicate that small radicals and formamide play a crucial role, in agreement with a number of recent experimental and theoretical results.

scholarly journals Direct and cost-efficient hyperpolarization of long-lived nuclear spin states on universal 15N2-diazirine molecular tags

2016 ◽  
Vol 2 (3) ◽  
pp. e1501438 ◽  
Author(s):  
Thomas Theis ◽  
Gerardo X. Ortiz ◽  
Angus W. J. Logan ◽  
Kevin E. Claytor ◽  
Yesu Feng ◽  
...  
Keyword(s):  
Nuclear Polarization ◽  
Molecular Function ◽  
Spin States ◽  
Time Constants ◽  
Biologically Relevant ◽  
Spin Order ◽  
Signal Decay ◽  
Wide Range ◽  
Cost Efficient ◽  
Biologically Relevant Molecules

Conventional magnetic resonance (MR) faces serious sensitivity limitations which can be overcome by hyperpolarization methods, but the most common method (dynamic nuclear polarization) is complex and expensive, and applications are limited by short spin lifetimes (typically seconds) of biologically relevant molecules. We use a recently developed method, SABRE-SHEATH, to directly hyperpolarize 15N2 magnetization and long-lived 15N2 singlet spin order, with signal decay time constants of 5.8 and 23 minutes, respectively. We find >10,000-fold enhancements generating detectable nuclear MR signals that last for over an hour. 15N2-diazirines represent a class of particularly promising and versatile molecular tags, and can be incorporated into a wide range of biomolecules without significantly altering molecular function.

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