scholarly journals Enzyvitands: evolvable biosynthetic and colorimetric chalices

2020 ◽  
Author(s):  
Thibaud Rossel ◽  
Bing Zhang ◽  
Raphael Gobat
Keyword(s):  
Chemical Synthesis ◽  
Small Molecules ◽  
Active Site ◽  
Chemical Sensor ◽  
Colorimetric Sensor ◽  
Selective Detection ◽  
X Ray ◽  
Naked Eye ◽  
Coordination Spheres

The literature is constellated with a wide variety of chemosensors against a plethora of analytes. This seminal library is used to inspire chemists to improve them using chemical synthesis. However, their optimization via chemical synthesis is a difficult task which takes time without the guarantee of final success.We show here that combinatorial chemistry,the use of first and second coordination spheres and the displacement of indicators united within a protein cavity offers an easy-to-assemble colorimetric bio-chemical sensor. It consists only of commercial chemicals. This colorimetric sensor is highly modular, cheap and evolvable. Its X-ray structure reveals the composition of its active site. This allows to design it rationally for the recognition of dopamine with the naked eye. Our bio-sensor therefore resembles a biological receptor for the recognition of neurotransmitters. Its immediate high adaptability and ability to be evolved can be useful for the selective detection of a wide variety of analytes going from small molecules to microorganisms. This discovery therefore makes it possible to dream of new biotechnological or new immunotherapeutic applications.<br>

scholarly journals Enzyvitands: evolvable biosynthetic and colorimetric chalices

2020 ◽  
Author(s):  
Thibaud Rossel ◽  
Bing Zhang ◽  
Raphael Gobat
Keyword(s):  
Chemical Synthesis ◽  
Small Molecules ◽  
Active Site ◽  
Chemical Sensor ◽  
Colorimetric Sensor ◽  
Selective Detection ◽  
X Ray ◽  
Naked Eye ◽  
Coordination Spheres

The literature is constellated with a wide variety of chemosensors against a plethora of analytes. This seminal library is used to inspire chemists to improve them using chemical synthesis. However, their optimization via chemical synthesis is a difficult task which takes time without the guarantee of final success.We show here that combinatorial chemistry,the use of first and second coordination spheres and the displacement of indicators united within a protein cavity offers an easy-to-assemble colorimetric bio-chemical sensor. It consists only of commercial chemicals. This colorimetric sensor is highly modular, cheap and evolvable. Its X-ray structure reveals the composition of its active site. This allows to design it rationally for the recognition of dopamine with the naked eye. Our bio-sensor therefore resembles a biological receptor for the recognition of neurotransmitters. Its immediate high adaptability and ability to be evolved can be useful for the selective detection of a wide variety of analytes going from small molecules to microorganisms. This discovery therefore makes it possible to dream of new biotechnological or new immunotherapeutic applications.<br>

scholarly journals Solving an X-Ray Structure of a Bio-Artificial Neurotransmitter Receptor Designed for the Naked-Eye Recognition of Dopamine

2020 ◽  
Author(s):  
Thibaud Rossel ◽  
Bing Zhang ◽  
Raphael Gobat
Keyword(s):  
Chemical Synthesis ◽  
Small Molecules ◽  
Active Site ◽  
Chemical Sensor ◽  
Selective Detection ◽  
Neurotransmitter Receptor ◽  
X Ray ◽  
Naked Eye ◽  
Coordination Spheres ◽  
Eye Recognition

The literature is constellated with a wide variety of chemosensors against a plethora of analytes. This seminal library is used to inspire chemists to improve them using chemical synthesis. However, their optimization via chemical synthesis is a difficult task which takes time without the guarantee of final success.We show here that combinatorial chemistry,the use of first and second coordination spheres and the displacement of indicators united within a protein cavity offers an easy-to-assemble colorimetric bio-chemical sensor. It consists only of commercial chemicals. This colorimetric sensor is highly modular, cheap and evolvable. Its X-ray structure reveals the composition of its active site. This allows to design it rationally for the recognition of dopamine with the naked eye. Our bio-sensor therefore resembles a biological receptor for the recognition of neurotransmitters. Its immediate high adaptability and ability to be evolved can be useful for the selective detection of a wide variety of analytes going from small molecules to microorganisms. This discovery therefore makes it possible to dream of new biotechnological or new immunotherapeutic applications.<br>

scholarly journals Solving an X-Ray Structure of a Bio-Artificial Neurotransmitter Receptor Designed for the Naked-Eye Recognition of Dopamine

2020 ◽  
Author(s):  
Thibaud Rossel ◽  
Bing Zhang ◽  
Raphael Gobat
Keyword(s):  
Chemical Synthesis ◽  
Small Molecules ◽  
Chemical Sensor ◽  
Selective Detection ◽  
Neurotransmitter Receptor ◽  
X Ray ◽  
Naked Eye ◽  
Coordination Spheres ◽  
Eye Recognition ◽  
New Applications

The literature is with a wide variety of against a plethora of . This seminal library is used to inspire chemists to improve them using chemical synthesis. However, their optimization via chemical synthesis is a difficult task which takes time without the guarantee of final success. We show here that chemistry, the use of first and second coordination spheres and the displacement of indicators united within a protein cavity offers an easy-to-assemble bio-chemical sensor. It consists only of commercial chemicals. This sensor is highly modular, cheap and . Its X-ray structure reveals the composition of its active site. This allows to design it rationally for the recognition of dopamine with the naked eye. Our bio-sensor therefore resembles a biological receptor for the recognition of neurotransmitters. Its immediate high adaptability and ability to be evolved can be useful for the selective detection of a wide variety of going from small molecules to microorganisms. This discovery therefore makes it possible to dream of new biotechnological or new applications.

scholarly journals Enzyvitands: evolvable biosynthetic and colorimetric chalices

2021 ◽  
Author(s):  
Thibaud Rossel ◽  
Bing Zhang ◽  
Raphael Gobat
Keyword(s):  
Small Molecules ◽  
Combinatorial Chemistry ◽  
Selective Detection ◽  
X Ray ◽  
Naked Eye ◽  
Coordination Spheres ◽  
Eye Recognition ◽  
Micro Organisms ◽  
Displacement Assays ◽  
Wide Assortment

<div><div><div><p>Designing the perfect sensor is the dream of any chemist. Since decades, a wide diversity of chemosensors targeting analytes has been explored in chemistry. Their chemical optimization is hard and with no guarantee of success. In this context, we propose a fast and easy-to-assemble colorimetric bio-chemical receptor coined Enzyvitand. It consists only of commercial chemicals. It relies on the reunification of combinatorial chemistry, first and second coordination spheres interactions and indicators displacement assays. All harbored within a protein cavity. The sensor is highly modular, cheap and evolvable. Thanks to its solved X-ray structure, we rationally designed it for the naked-eye recognition of dopamine. Hence, our sensor imitates a biological receptor for the recognition of neurotransmitters. Its immediate high versatility and evolvability is valuable for the selective detection of a wide assortment of analytes from small molecules up to micro-organisms. For the future, we anticipate new biotechnological or immunotherapeutic applications of our bio-sensor.</p></div></div></div>

scholarly journals Enzyvitands: versatile evolvable colorimetric chembioreceptors

2021 ◽  
Author(s):  
Thibaud Rossel ◽  
zhang Bing ◽  
Raphael Gobat
Keyword(s):  
Small Molecules ◽  
Complex Samples ◽  
X Ray ◽  
Naked Eye ◽  
Self Assembling ◽  
Coordination Spheres ◽  
Eye Recognition ◽  
Micro Organisms ◽  
Displacement Assays ◽  
Wide Assortment

Designing the perfect sensor is the dream of any chemist. Since decades, a wide diversity of synthetic receptors targeting analytes has been explored in chemistry. Their chemical optimization is hard and with no guarantee of success. In this context, we propose a fast and self assembling colorimetric bio-chemical receptor coined Enzyvitand. It consists only of commercial chemicals. It relies on the reunification of combinatorial chemistry , first and second coordination spheres interactions and indicators displacement assays. All harbored within a protein cavity. The sensor is highly modular, cheap and evolvable. Thanks to its solved X-ray structure, we rationally designed it for the selectiv naked-eye recognition of dopamine over other neutrotransmitters through second coordination sphere. Hence, our sensor imitates a biological receptor for the recognition of neurotransmitters. Finally, it works in complex samples such as urine. Its immediate high versatility and evolvability is valuable for the selective detection of a wide assortment of analytes from small molecules up to micro-organisms. For the future, we anticipate new biotechnological or immunotherapeutic applications of our synthetic oligomer.

scholarly journals High-performance, quantum mechanics-based macromolecular x-ray refinement

2014 ◽  
Vol 70 (a1) ◽  
pp. C1446-C1446
Author(s):  
Oleg Borbulevych ◽  
Lance Westerhoff
Keyword(s):  
Quantum Mechanics ◽  
Active Site ◽  
High Performance ◽  
Covalent Bonds ◽  
Metal Centers ◽  
X Ray ◽  
Design And Optimization ◽  
Surrounding Structure ◽  
Lower Strain ◽  
Coordination Spheres

"Modern, structure based drug discovery (SBDD) is dependent upon accurate protein:ligand structure determination and characterization. In conventional x-ray refinement, the geometry of the ligand within the active site is modeled according to the practitioner's beliefs as expressed in the form of stereochemical restraints provided by the ligand library or CIF file. Further, metal centers, bound species, and so on can be difficult to refine correctly without significant human intervention. Our work has addressed this problem through the integration of DivCon6 - a linear scaling, semiempirical, quantum mechanics (SE-QM) functional - with the Phenix refinement package. With Phenix/DivCon[1], SE-QM is used in ""real-time"" during each microcycle over the course of the refinement. With its inclusion of electrostatics, charge transfer, polarization, dispersion, hydrogen bonds, etcetera, this method is a much more rigorous, robust alternative to conventional stereochemical restraints and is better able to accurately model protein:ligand structures without ""tweaking"" any restraints. We report PM6 refinement results for several key examples including structures with metal coordination spheres, covalent bonds, and other exotic protein:ligand chemistry situations. When compared with the originally deposited PDB structures, we found in all cases that QM refinement leads to ligand structures with much lower strain, and in some cases, the improvement is dramatic and as much 10+ fold. At the same time, SE-QM methods are better able to capture the influence of the surrounding structure (e.g. active site) on the ligand. These interactions are particularly interesting in SBDD as they are often the targets for lead design and optimization, and examples that illustrate how these interactions are captured with SE-QM will also be discussed."

scholarly journals Rapid and selective detection of aluminum ion using 1,2,3-triazole-4,5-dicarboxylic acid-functionalized gold nanoparticle-based colorimetric sensor

RSC Advances ◽  
2021 ◽  
Vol 11 (49) ◽  
pp. 30635-30645
Author(s):  
Shengliang Zhao ◽  
Liqiong Chen ◽  
Feiyan Liu ◽  
Yongyao Fan ◽  
Yiheng Liu ◽  
...  
Keyword(s):  
Dicarboxylic Acid ◽  
Gold Nanoparticle ◽  
Colorimetric Sensor ◽  
Selective Detection ◽  
Aluminum Ion ◽  
Naked Eye ◽  
Vis Spectroscopy ◽  
Rapid Quantification

A colorimetric sensor based on TADA–AuNPs accompanied by a masking agent DPC was constructed, with which the rapid quantification of Al3+ can be realized by UV-vis spectroscopy or naked eye observation.

The structure of chitinases and prospects for structure-based drug design

1995 ◽  
Vol 73 (S1) ◽  
pp. 1142-1146 ◽  
Author(s):  
Jon D. Robertus ◽  
P. John Hart ◽  
Arthur F. Monzingo ◽  
Edward Marcotte ◽  
Thomas Hollis
Keyword(s):  
Drug Design ◽  
Small Molecules ◽  
Mechanism Of Action ◽  
Active Site ◽  
Antifungal Agents ◽  
Structure Based Drug Design ◽  
X Ray ◽  
Class Ii Chitinase ◽  
Transition State Geometry ◽  
Chitinase Inhibitors

Many fungi, including pathogenic strains, require proper chitin metabolism to assure normal cell wall replication. Chitinase hydrolyzes chitin; inhibition of endogenous chitinases or application of extracellular chitinases can disrupt fungal division. It is possible that chitinase inhibitors could be used as antifungal agents. We have solved the X-ray structure of a class II chitinase from barley and proposed a mechanism of action. The enzyme has a structural core similar to lysozyme and probably acts in a similar catalytic manner. The enzyme structure can, in principle, be used to identify small molecules that will bind avidly to the active site and act as inhibitors. Those inhibitors that embody transition state geometry are likely to be particularly effective. Key words: chitinase, mechanism of action, drug design.

Xenon Trioxide Adducts of O-Donor Ligands; [(CH3)2CO]3XeO3, [(CH3)2SO]3(XeO3)2, (C5H5NO)3(XeO3)2, and [(C6H5)3PO]2XeO3

2018 ◽  
Author(s):  
Katherine Marczenko ◽  
James Goettel ◽  
Gary Schrobilgen
Keyword(s):  
Room Temperature ◽  
Triphenylphosphine Oxide ◽  
Donor Ligands ◽  
Mechanical Shock ◽  
X Ray Diffraction ◽  
X Ray ◽  
Oxygen Coordination ◽  
Xenon Trioxide ◽  
Distorted Octahedra ◽  
Coordination Spheres

Oxygen coordination to the Xe(VI) atom of XeO<sub>3</sub> was observed in its adducts with triphenylphosphine oxide, dimethylsulfoxide, pyridine-N-oxide, and acetone. The crystalline adducts were characterized by low-temperature, single-crystal X-ray diffraction and Raman spectroscopy. Unlike solid XeO<sub>3</sub>, which detonates when mechanically or thermally shocked, the solid [(C<sub>6</sub>H<sub>5</sub>)<sub>3</sub>PO]<sub>2</sub>XeO<sub>3</sub>, [(CH<sub>3</sub>)<sub>2</sub>SO]<sub>3</sub>(XeO<sub>3</sub>)<sub>2</sub>,<sub> </sub>and (C<sub>5</sub>H<sub>5</sub>NO)<sub>3</sub>(XeO<sub>3</sub>)<sub>2</sub> adducts are insensitive to mechanical shock, but undergo rapid deflagration when ignited by a flame. Both [(C<sub>6</sub>H<sub>5</sub>)<sub>3</sub>PO]<sub>2</sub>XeO<sub>3 </sub>and (C<sub>5</sub>H<sub>5</sub>NO)<sub>3</sub>(XeO<sub>3</sub>)<sub>2</sub> are air-stable whereas [(CH<sub>3</sub>)<sub>2</sub>SO]<sub>3</sub>(XeO<sub>3</sub>)<sub>2</sub> slowly decomposes over several days and [(CH<sub>3</sub>)<sub>2</sub>CO]<sub>3</sub>XeO<sub>3</sub> undergoes adduct dissociation at room temperature. The xenon coordination sphere of [(C<sub>6</sub>H<sub>5</sub>)<sub>3</sub>PO]<sub>2</sub>XeO<sub>3</sub> is a distorted square pyramid which provides the first example of a five-coordinate XeO<sub>3</sub> adduct. The xenon coordination spheres of the remaining adducts are distorted octahedra comprised of three Xe---O secondary contacts that are approximately trans to the primary Xe–O bonds of XeO<sub>3</sub>. Quantum-chemical calculations were used to assess the Xe---O adduct bonds, which are predominantly electrostatic σ-hole bonds between the nucleophilic oxygen atoms of the bases and the σ-holes of the xenon atoms.

Computationally Augmented Retrosynthesis: Total Synthesis of Paspaline A and Emindole PB

2018 ◽  
Author(s):  
Timothy Newhouse ◽  
Daria E. Kim ◽  
Joshua E. Zweig
Keyword(s):  
Chemical Synthesis ◽  
Total Synthesis ◽  
Small Molecules ◽  
First Principles ◽  
Quantum Chemical ◽  
Computational Analysis ◽  
Empirical Evaluation ◽  
Synthetic Strategy ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions

The diverse molecular architectures of terpene natural products are assembled by exquisite enzyme-catalyzed reactions. Successful recapitulation of these transformations using chemical synthesis is hard to predict from first principles and therefore challenging to execute. A means of evaluating the feasibility of such chemical reactions would greatly enable the development of concise syntheses of complex small molecules. Herein, we report the computational analysis of the energetic favorability of a key bio-inspired transformation, which we use to inform our synthetic strategy. This approach was applied to synthesize two constituents of the historically challenging indole diterpenoid class, resulting in a concise route to (–)-paspaline A in 9 steps from commercially available materials and the first pathway to and structural confirmation of emindole PB in 13 steps. This work highlights how traditional retrosynthetic design can be augmented with quantum chemical calculations to reveal energetically feasible synthetic disconnections, minimizing time-consuming and expensive empirical evaluation.

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