scholarly journals Chloromethyl Acryl Reagents for Simple and Site-Selective Cysteine and Disulfide Modification

2021 ◽  
Author(s):  
Lujuan Xu ◽  
Seah Ling Kuan ◽  
Tanja Weil
Keyword(s):  
Protein Modification ◽  
High Efficiency ◽  
Chemical Properties ◽  
Hydroxyl Group ◽  
One Pot ◽  
Synthetic Drugs ◽  
Protein Conjugates ◽  
Ester Linkage ◽  
Protein Biotherapeutics ◽  
Site Selective

The generation of protein biotherapeutics with improved features compared to the synthetic drugs has received emerging interest. The conjugation of various synthetic functionalities to proteins provides access to new classes of protein conjugates, where the advantages from both the synthetic world and Nature can be combined in a synergistic fashion. Here, we reported that 2-chloromethyl acryl scaffold can serve as a simple yet versatile platform for synthesizing acrylamide or acrylate derivatives by coupling with different end-group functionalities (amino group or hydroxyl group) via a one-pot reaction. The chemical properties of the amide or ester linkage influence their inherent reactivity as bioconjugation reagents, which in turn allows synthetic customization of their features to achieve selective protein modification at cysteine or disulfide sites on demand. 2-Chloromethyl acrylamide reagents with amide linkage favors selective modification at cysteine site with high efficiency and the resultant bioconjugates exhibit superior stability compared to commonly employed maleimide-thiol conjugates. In contrast, 2-chloromethyl acrylate reagents bearing ester linkage can undergo two successive Michael reaction, allowing the selective modification of disulfides with high labelling efficiency and conjugate stability. These reagents could outperform widely applied maleimide reagents in terms of stability of the resultant bioconjugates without compromising on the ease of reagent preparation, reactivity and reaction speed. <br>

scholarly journals Chloromethyl Acryl Reagents for Simple and Site-Selective Cysteine and Disulfide Modification

2021 ◽  
Author(s):  
Lujuan Xu ◽  
Seah Ling Kuan ◽  
Tanja Weil
Keyword(s):  
Protein Modification ◽  
High Efficiency ◽  
Chemical Properties ◽  
Hydroxyl Group ◽  
One Pot ◽  
Synthetic Drugs ◽  
Protein Conjugates ◽  
Ester Linkage ◽  
Protein Biotherapeutics ◽  
Site Selective

The generation of protein biotherapeutics with improved features compared to the synthetic drugs has received emerging interest. The conjugation of various synthetic functionalities to proteins provides access to new classes of protein conjugates, where the advantages from both the synthetic world and Nature can be combined in a synergistic fashion. Here, we reported that 2-chloromethyl acryl scaffold can serve as a simple yet versatile platform for synthesizing acrylamide or acrylate derivatives by coupling with different end-group functionalities (amino group or hydroxyl group) via a one-pot reaction. The chemical properties of the amide or ester linkage influence their inherent reactivity as bioconjugation reagents, which in turn allows synthetic customization of their features to achieve selective protein modification at cysteine or disulfide sites on demand. 2-Chloromethyl acrylamide reagents with amide linkage favors selective modification at cysteine site with high efficiency and the resultant bioconjugates exhibit superior stability compared to commonly employed maleimide-thiol conjugates. In contrast, 2-chloromethyl acrylate reagents bearing ester linkage can undergo two successive Michael reaction, allowing the selective modification of disulfides with high labelling efficiency and conjugate stability. These reagents could outperform widely applied maleimide reagents in terms of stability of the resultant bioconjugates without compromising on the ease of reagent preparation, reactivity and reaction speed. <br>

Chemoselective and site-selective peptide and native protein modification enabled by aldehyde auto-oxidation

2017 ◽  
Vol 53 (5) ◽  
pp. 959-962 ◽  
Author(s):  
Landa Purushottam ◽  
Srinivasa Rao Adusumalli ◽  
Maheshwerreddy Chilamari ◽  
Vishal Rai
Keyword(s):  
Protein Modification ◽  
Lysine Residue ◽  
Chemical Technology ◽  
Single Site ◽  
Native Protein ◽  
Protein Backbone ◽  
Precision Engineering ◽  
One Pot ◽  
Site Selective

Chemical technology delivers precision engineering of the native protein backbone. A lysine residue undergoes single-site formylation or acylation in a multi-step yet operationally simple one-pot process.

Systematic Engineering of a Protein Nanocage for High-Yield, Site-Specific Modification

2018 ◽  
Author(s):  
Daniel D. Brauer ◽  
Emily C. Hartman ◽  
Daniel L.V. Bader ◽  
Zoe N. Merz ◽  
Danielle Tullman-Ercek ◽  
...  
Keyword(s):  
Small Molecules ◽  
Protein Modification ◽  
Positive Charge ◽  
Specific Protein ◽  
High Yield ◽  
Site Specific ◽  
Protein Cage ◽  
Protein Carriers ◽  
Site Selective ◽  
Targeted Library

<div> <p>Site-specific protein modification is a widely-used strategy to attach drugs, imaging agents, or other useful small molecules to protein carriers. N-terminal modification is particularly useful as a high-yielding, site-selective modification strategy that can be compatible with a wide array of proteins. However, this modification strategy is incompatible with proteins with buried or sterically-hindered N termini, such as virus-like particles like the well-studied MS2 bacteriophage coat protein. To assess VLPs with improved compatibility with these techniques, we generated a targeted library based on the MS2-derived protein cage with N-terminal proline residues followed by three variable positions. We subjected the library to assembly, heat, and chemical selections, and we identified variants that were modified in high yield with no reduction in thermostability. Positive charge adjacent to the native N terminus is surprisingly beneficial for successful extension, and over 50% of the highest performing variants contained positive charge at this position. Taken together, these studies described nonintuitive design rules governing N-terminal extensions and identified successful extensions with high modification potential.</p> </div>

Chlorosulfonic Acid Supported Piperidine-4-carboxylic Acid (PPCA) Functionalized Fe3O4 Nanoparticles (Fe3O4-PPCA): The Efficient, Green and Reusable Nanocatalyst for the Synthesis of Pyrazolyl Coumarin Derivatives under Solvent-Free Conditions

2019 ◽  
Vol 22 (2) ◽  
pp. 123-128
Author(s):  
Setareh Habibzadeh ◽  
Hassan Ghasemnejad-Bosra ◽  
Mina Haghdadi ◽  
Soheila Heydari-Parastar
Keyword(s):  
Carboxylic Acid ◽  
Fe3o4 Nanoparticles ◽  
High Efficiency ◽  
Reaction Times ◽  
Chlorosulfonic Acid ◽  
Aromatic Aldehydes ◽  
Solvent Free ◽  
Magnetic Nanocatalyst ◽  
One Pot ◽  
Solvent Free Conditions

Background: In this study, we developed a convenient methodology for the synthesis of coumarin linked to pyrazolines and pyrano [2,3-h] coumarins linked to 3-(1,5-diphenyl-4,5- dihydro-1H-pyrazol-3-yl)-chromen-2-one derivatives using Chlorosulfonic acid supported Piperidine-4-carboxylic acid (PPCA) functionalized Fe3O4 nanoparticles (Fe3O4-PPCA) catalyst. Materials and Methods:: Fe3O4-PPCA was investigated as an efficient and magnetically recoverable Nanocatalyst for the one-pot synthesis of substituted coumarins from the reaction of coumarin with a variety of aromatic aldehydes in high to excellent yield at room temperature under solvent-free conditions. The magnetic nanocatalyst can be easily recovered by applying an external magnet device and reused for at least 10 reaction runs without considerable loss of reactivity. Results and Conclusion: The advantages of this protocol are the use of commercially available materials, simple and an inexpensive procedure, easy separation, and an eco-friendly procedure, and it shows good reaction times, good to high yields, inexpensive and practicability procedure, and high efficiency.

scholarly journals An efficient and practical chemo-enzymatic route to (3R,3aR,6R,6aR)-hexahydrofuro[3,2-b]furan-6-amino-3-ol (6-aminoisomannide) from renewable sources

SynOpen ◽  
2021 ◽  
Author(s):  
Valerio Zullo ◽  
Antonella Petri ◽  
Anna Iuliano
Keyword(s):  
Hydroxy Group ◽  
Sodium Azide ◽  
Hydroxyl Group ◽  
Azido Group ◽  
One Pot ◽  
Renewable Sources ◽  
Nucleophilic Displacement ◽  
Trifluoromethanesulfonic Anhydride ◽  
Enzymatic Route

The synthesis of 6-aminoisomannide is easily achieved starting from the renewable, inexpensive and commercially available isosorbide, in 66% overall yield. A biocatalysed highly regioselective acetylation of the 3-endo hydroxyl group of isosorbide was followed by the stereospecific interconversion of the 6-exo hydroxyl group into azido group, through reaction with trifluoromethanesulfonic anhydride followed by nucleophilic displacement of the triflate group by sodium azide. Finally, reduction of the azido group and deacetylation of the 3-hydroxy group were performed one pot by using LiAlH4.

Fast and high-efficiency synthesis of 2-substituted benzothiazoles via combining enzyme catalysis and photoredox catalysis in one-pot

2020 ◽  
pp. 104607
Author(s):  
Zeng-Jie Yang ◽  
Qing-Tian Gong ◽  
Yuan Yu ◽  
Wei-Fan Lu ◽  
Zhe-Ning Wu ◽  
...  
Keyword(s):  
Enzyme Catalysis ◽  
High Efficiency ◽  
Photoredox Catalysis ◽  
One Pot

Recent advance in ester synthesis by Multi Component Reactions (MCRs): A Review

2021 ◽  
Vol 25 ◽  
Author(s):  
Dhaval B. Patel ◽  
Jagruti A. Parmar ◽  
Siddharth S. Patel ◽  
Unnati J. Naik ◽  
Hitesh D. Patel
Keyword(s):  
Multicomponent Reactions ◽  
Medicinal Chemistry ◽  
Reaction Times ◽  
Synthetic Methods ◽  
Ester Synthesis ◽  
One Pot ◽  
Wide Range ◽  
Recent Developments ◽  
Ester Linkage ◽  
The One

: The synthesis of ester containing heterocyclic compounds via multicomponent reaction is one of the most preferable process in the synthetic organic chemistry and medicinal chemistry. Compounds containing ester linkage have a wide range of biological application in the pharmaceutical field. Therefore, many method have been developed for the synthesis of these type of derivatives. However, some of them are carried out in the presence of toxic solvents and catalysts, with lower yields, longer reaction times, low selectivities and by-products. Thus, the development of new synthetic methods for the ester synthesis is required in the medicinal chemistry. As we know, multicomponent reactions (MCRs) are a powerful tool towards the one-pot ester synthesis, so in this article we have reviewed the recent developments in ester synthesis. This work covers selected explanation of methods via multicomponent reactions to explore the methodological development in ester synthesis.

scholarly journals Synthesis and Characterizations of Dipeptide Derivative of Gentamicin

2019 ◽  
Vol 28 (2) ◽  
pp. 73-82
Author(s):  
Oun D. Khudair ◽  
Diar A. Fatih
Keyword(s):  
Acid Chloride ◽  
Solution Method ◽  
Hydroxyl Group ◽  
Hydroxyl Groups ◽  
Free Hydroxyl ◽  
Ester Linkage ◽  
Amine Groups ◽  
Conventional Solution ◽  
Dipeptide Derivative

Abstract       The target derivative are gentamicin linked with L-Val- L-Ala by an ester linkage. These were synthesized by esterification method, which included the reaction of -OH hydroxyl group on (carbon No.5) of gentamicin with the acid chloride of the corresponding dipeptide, The preparation of new derivative of gentamicin involved protected the primary & secondary amine groups of Gentamicin, by Ethylchloroformate (ECF) to give N-carbomethoxy Gentamicin which was used for further chemical synthesis involving the free hydroxyl groups. Then prepared dipeptide (L-Val- L-Ala) by conventional solution method in present DCC & HoBt then reacted with thionyl chloride to prepared acid chloride of dipeptides, then after, linked by ester linkage to N-protection gentamicin in present pyridine as base, finally deportation the amino group of synthesized compound by using TFAA in present anisole. The characterization of the titled compounds were performed utilizing FTIR spectroscopy, CHNS elemental analysis, and by measurements of their physical properties.  

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