scholarly journals Chiroptical activity of hydroxycarboxylic acids with implications for the origin of biological homochirality

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jana Bocková ◽  
Nykola C. Jones ◽  
Uwe J. Meierhenrich ◽  
Søren V. Hoffmann ◽  
Cornelia Meinert
Keyword(s):  
Amino Acids ◽  
Lactic Acid ◽  
Organic Molecules ◽  
Building Blocks ◽  
Aliphatic Chain ◽  
Monocarboxylic Acids ◽  
Hydroxycarboxylic Acids ◽  
Polarised Light ◽  
Suitable Target ◽  
Anisotropy Spectra

AbstractCircularly polarised light (CPL) interacting with interstellar organic molecules might have imparted chiral bias and hence preluded prebiotic evolution of biomolecular homochirality. The l-enrichment of extra-terrestrial amino acids in meteorites, as opposed to no detectable excess in monocarboxylic acids and amines, has previously been attributed to their intrinsic interaction with stellar CPL revealed by substantial differences in their chiroptical signals. Recent analyses of meteoritic hydroxycarboxylic acids (HCAs) – potential co-building blocks of ancestral proto-peptides – indicated a chiral bias toward the l-enantiomer of lactic acid. Here we report on novel anisotropy spectra of several HCAs using a synchrotron radiation electronic circular dichroism spectrophotometer to support the re-evaluation of chiral biomarkers of extra-terrestrial origin in the context of absolute photochirogenesis. We found that irradiation by CPL which would yield l-excess in amino acids would also yield l-excess in aliphatic chain HCAs, including lactic acid and mandelic acid, in the examined conditions. Only tartaric acid would show “unnatural” d-enrichment, which makes it a suitable target compound for further assessing the relevance of the CPL scenario.

scholarly journals Chiroptical activity of hydroxycarboxylic acids: implications for the origin of biological homochirality

2021 ◽  
Author(s):  
Jana Bocková ◽  
Nykola Jones ◽  
Uwe Meierhenrich ◽  
Søren Hoffmann ◽  
Cornelia Meinert
Keyword(s):  
Amino Acids ◽  
Lactic Acid ◽  
Enantiomeric Excess ◽  
Building Blocks ◽  
Aliphatic Chain ◽  
Monocarboxylic Acids ◽  
Hydroxycarboxylic Acids ◽  
Polarised Light ◽  
Suitable Target ◽  
Anisotropy Spectra

Abstract Circularly polarised light (CPL) interacting with interstellar organic molecules might have imparted chiral bias and hence preluded prebiotic evolution of biomolecular homochirality. The l-enrichment of extra-terrestrial amino acids in meteorites, as opposed to no detectable excess in monocarboxylic acids and amines, has previously been attributed to their intrinsic interaction with stellar CPL revealed by substantial differences in their chiroptical signals. Recent analyses of meteoritic hydroxycarboxylic acids (HCAs) – potential co-building blocks of ancestral proto-peptides – showed an enantiomeric excess in l-lactic acid. Here we report on novel anisotropy spectra of several HCAs using a synchrotron radiation electronic circular dichroism spectrophotometer to support the re-evaluation of chiral biomarkers of extra-terrestrial origin in the context of absolute photochirogenesis. We found that irradiation by CPL which would yield l-excess in amino acids would also yield lexcess in aliphatic chain HCAs including lactic acid as well as mandelic acid in the examined conditions. Only tartaric acid would show “unnatural” d-enrichment, which makes it a suitable target compound for further assessing the relevance of the CPL scenario.

scholarly journals Synthesis and Preservation of Organic Molecules with Homochiral Excess by Adsorption on Carbon in Carbonaceous Chondrites

2021 ◽  
pp. 46-53
Author(s):  
V. M. Zhmakin
Keyword(s):  
Carbon Dioxide ◽  
Amino Acids ◽  
Carbon Monoxide ◽  
Lactic Acid ◽  
Organic Synthesis ◽  
Organic Molecules ◽  
Early Earth ◽  
Carbonaceous Chondrites ◽  
Abiogenic Synthesis ◽  
Extraterrestrial Origin

The nature of carbon, initial components, molecules of homochiral abiogenic synthesis and their preservation from decay and racemization for more than 4.5 billion years in carbonaceous chondrites has not been established. In the oxygen-free atmospheres of the nebula and early Earth, hydrogen and hydrogen-containing gases were oxidized with carbon monoxide and carbon dioxide to form carbon and water, as well as the intermediates of these reactions, formaldehyde and methane acid. Together with ammonia, they were the initial components of organic synthesis. According to the Rebinder rule, carbon adsorbs hydrogen well, including in organic molecules. In this connection, experiments with the assumed conditions of the early Earth were carried out by adsorption on carbon to obtain R-(rectus, Latin) ribose from formaldehyde, and S-(sinister) serine from formaldehyde, methane acid and ammonia. For other S-amino acids, a stereo chemical justification of their formation based on S-serine is given. For carbonaceous chondrites, the results of the above experiments were confirmed by the correlation of an increase in homochiral excess with an increase in the amount of hydrogen in aldonic acids and lactic acid with a coefficient of 0.94 and 0.85 in amino acids. The justification of the homochiral process will reduce the costs of searching for life on planets, for scientific research, for the production of medicines, perfumes, food, and so on. Doubts about the extraterrestrial origin of homochiral enantiomers in carbonaceous chondrites arise most often due to a lack of understanding of the reasons for their appearance. This work will significantly reduce such skepticism.

Amino Acids and Proteins from Fossils

1988 ◽  
Vol 1 ◽  
pp. 20-33 ◽  
Author(s):  
Gordon B. Curry
Keyword(s):  
Amino Acids ◽  
Relative Stability ◽  
Fossil Record ◽  
Organic Molecules ◽  
Soft Tissues ◽  
Building Blocks ◽  
Biological Molecules ◽  
Long Term Stability ◽  
Living Organisms

The fossilization potential of organic molecules is extremely variable. Some organic compounds which are very common in living organisms are extremely rare in the fossil record, and are only preserved under exceptional conditions. For example DNA, despite its abundance in living organisms, is apparently only rarely preserved in recognizable form as fossils, primarily because it is concentrated in vulnerable soft-tissues, and the molecule itself is highly reactive and therefore easily broken down. In contrast the recognizable remains of molecules such as proteins, lipids and certain pigments are extremely abundant in the fossil record, to the extent that a group of fossilized molecules derived from bacterial cell walls is present in quantities which exceed that of the total organic carbon in the present day biosphere. Such preservation reflects the inherent relative stability of the molecular structure, or at least the relative stability of the building blocks of which it is constructed. Even simple biological molecules tend to be constructed from smaller molecular subunits, and their long-term stability, and ultimately their fossilization potential, depends both on the strength of the bonding between these smaller modular building blocks as well as on the durability of the building blocks themselves if they become dissociated during or after fossilization. As would be expected from their geological record, the constituent nucleic acids of DNA are much less stable than the amino acids which make up proteins.

scholarly journals A Sustainable Improvement of ω-Bromoalkylphosphonates Synthesis to Access Novel KuQuinones

Organics ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 107-117
Author(s):  
Mattia Forchetta ◽  
Valeria Conte ◽  
Giulia Fiorani ◽  
Pierluca Galloni ◽  
Federica Sabuzi
Keyword(s):  
Metal Oxides ◽  
Phosphonic Acid ◽  
Organic Molecules ◽  
Building Blocks ◽  
Reaction Conditions ◽  
Phosphonic Acids ◽  
Sustainable Improvement ◽  
Phosphonate Esters ◽  
First Time ◽  
Complex Organic

Owing to the attractiveness of organic phosphonic acids and esters in the pharmacological field and in the functionalization of conductive metal-oxides, the research of effective synthetic protocols is pivotal. Among the others, ω-bromoalkylphosphonates are gaining particular attention because they are useful building blocks for the tailored functionalization of complex organic molecules. Hence, in this work, the optimization of Michaelis–Arbuzov reaction conditions for ω-bromoalkylphosphonates has been performed, to improve process sustainability while maintaining good yields. Synthesized ω-bromoalkylphosphonates have been successfully adopted for the synthesis of new KuQuinone phosphonate esters and, by hydrolysis, phosphonic acid KuQuinone derivatives have been obtained for the first time. Considering the high affinity with metal-oxides, KuQuinones bearing phosphonic acid terminal groups are promising candidates for biomedical and photo(electro)chemical applications.

scholarly journals Peculiarities of promiscuous l-threonine transaldolases for enantioselective synthesis of β-hydroxy-α-amino acids

2021 ◽  
Author(s):  
Shan Wang ◽  
Hai Deng
Keyword(s):  
Amino Acids ◽  
Organic Molecules ◽  
Stereoselective Synthesis ◽  
Enantioselective Synthesis ◽  
General Mechanism ◽  
Future Developments ◽  
Key Points ◽  
Biomaterial Science ◽  
One Step ◽  
Harsh Conditions

Abstract The introduction of β-hydroxy-α-amino acids (βHAAs) into organic molecules has received considerable attention as these molecules have often found widespread applications in bioorganic chemistry, medicinal chemistry and biomaterial science. Despite innovation of asymmetric synthesis of βHAAs, stereoselective synthesis to control the two chiral centres at Cα and Cβ positions is still challenging, with poor atomic economy and multi protection and deprotection steps. These syntheses are often operated under harsh conditions. Therefore, a biotransformation approach using biocatalysts is needed to selectively introduce these two chiral centres into structurally diverse molecules. Yet, there are few ways that enable one-step synthesis of βHAAs. One is to extend the substrate scope of the existing enzyme inventory. Threonine aldolases have been explored to produce βHAAs. However, the enzymes have poor controlled installation at Cβ position, often resulting in a mixture of diastereoisomers which are difficult to be separated. In this respect, l-threonine transaldolases (LTTAs) offer an excellent potential as the enzymes often provide controlled stereochemistry at Cα and Cβ positions. Another is to mine LTTA homologues and engineer the enzymes using directed evolution with the aim of finding engineered biocatalysts to accept broad substrates with enhanced conversion and stereoselectivity. Here, we review the development of LTTAs that incorporate various aldehyde acceptors to generate structurally diverse βHAAs and highlight areas for future developments. Key points • The general mechanism of the transaldolation reaction catalysed by LTTAs • Recent advances in LTTAs from different biosynthetic pathways • Applications of LTTAs as biocatalysts for production of βHAAs

scholarly journals Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4587
Author(s):  
Fanny d’Orlyé ◽  
Laura Trapiella-Alfonso ◽  
Camille Lescot ◽  
Marie Pinvidic ◽  
Bich-Thuy Doan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Biomedical Applications ◽  
Chemical Reactivity ◽  
Physical Stability ◽  
Chemical Properties ◽  
Building Blocks ◽  
Imaging Probes ◽  
Therapeutic Molecules

There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.

scholarly journals Lactate oxidative phosphorylation by annulus fibrosus cells: evidence for lactate-dependent metabolic symbiosis in intervertebral discs

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Dong Wang ◽  
Robert Hartman ◽  
Chao Han ◽  
Chao-ming Zhou ◽  
Brandon Couch ◽  
...  
Keyword(s):  
Amino Acids ◽  
Lactic Acid ◽  
Oxidative Phosphorylation ◽  
Intervertebral Disc ◽  
Annulus Fibrosus ◽  
Tca Cycle ◽  
Heavy Isotope ◽  
In Vivo Models ◽  
Disc Tissue ◽  
Tca Cycle Intermediates

Abstract Background Intervertebral disc degeneration contributes to low back pain. The avascular intervertebral disc consists of a central hypoxic nucleus pulpous (NP) surrounded by the more oxygenated annulus fibrosus (AF). Lactic acid, an abundant end-product of NP glycolysis, has long been viewed as a harmful waste that acidifies disc tissue and decreases cell viability and function. As lactic acid is readily converted into lactate in disc tissue, the objective of this study was to determine whether lactate could be used by AF cells as a carbon source rather than being removed from disc tissue as a waste byproduct. Methods Import and conversion of lactate to tricarboxylic acid (TCA) cycle intermediates and amino acids in rabbit AF cells were measured by heavy-isotope (13C-lactate) tracing experiments using mass spectrometry. Levels of protein expression of lactate converting enzymes, lactate importer and exporter in NP and AF tissues were quantified by Western blots. Effects of lactate on proteoglycan (35S-sulfate) and collagen (3H-proline) matrix protein synthesis and oxidative phosphorylation (Seahorse XFe96 Extracellular Flux Analyzer) in AF cells were assessed. Results Heavy-isotope tracing experiments revealed that AF cells imported and converted lactate into TCA cycle intermediates and amino acids using in vitro cell culture and in vivo models. Addition of exogenous lactate (4 mM) in culture media induced expression of the lactate importer MCT1 and increased oxygen consumption rate by 50%, mitochondrial ATP-linked respiration by 30%, and collagen synthesis by 50% in AF cell cultures grown under physiologic oxygen (2-5% O2) and glucose concentration (1-5 mM). AF tissue highly expresses MCT1, LDH-H, an enzyme that preferentially converts lactate to pyruvate, and PDH, an enzyme that converts pyruvate to acetyl-coA. In contrast, NP tissue highly expresses MCT4, a lactate exporter, and LDH-M, an enzyme that preferentially converts pyruvate to lactate. Conclusions These findings support disc lactate-dependent metabolic symbiosis in which lactate produced by the hypoxic, glycolytic NP cells is utilized by the more oxygenated AF cells via oxidative phosphorylation for energy and matrix production, thus shifting the current research paradigm of viewing disc lactate as a waste product to considering it as an important biofuel. These scientifically impactful results suggest novel therapeutic targets in disc metabolism and degeneration.

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