scholarly journals Formation Mechanism and Biomedical Applications of Protease-Manipulated Peptide Assemblies

2021 ◽  
Vol 9 ◽  
Author(s):  
Tianyue Jiang ◽  
Chendan Liu ◽  
Xiao Xu ◽  
Bingfang He ◽  
Ran Mo
Keyword(s):  
Biomedical Applications ◽  
Enzymatic Catalysis ◽  
Building Blocks ◽  
Molecular Assembly ◽  
Bond Forming ◽  
Peptide Assembly ◽  
Non Covalent Interactions ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions ◽  
Matrix Construction

Exploiting enzyme-catalyzed reactions to manipulate molecular assembly has been considered as an attractive bottom-up nanofabrication approach to developing a variety of nano-, micro-, and macroscale structures. Upon enzymatic catalysis, peptides and their derivatives transform to assemblable building blocks that form ordered architecture by non-covalent interactions. The peptide assemblies with unique characteristics have great potential for applications in bionanotechnology and biomedicine. In this mini review, we describe typical mechanisms of the protease-instructed peptide assembly via bond-cleaving or bond-forming reactions, and outline biomedical applications of the peptide assemblies, such as drug depot, sustained release, controlled release, gelation-regulated cytotoxicity, and matrix construction.

Probing non-covalent interactions driving molecular assembly in organo-electronic building blocks

CrystEngComm ◽  
2019 ◽  
Vol 21 (20) ◽  
pp. 3151-3157 ◽  
Author(s):  
Sarah N. Johnson ◽  
Thomas L. Ellington ◽  
Duong T. Ngo ◽  
Jorge L. Nevarez ◽  
Nicholas Sparks ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Density Functional ◽  
Building Blocks ◽  
Molecular Assembly ◽  
Functional Theory ◽  
X Ray ◽  
X Ray Crystallography ◽  
Non Covalent Interactions ◽  
Density Functional Theory Computations ◽  
Covalent Interactions

One co-crystal structure characterized to identify and quantify various non-covalent interactions with spectroscopy, X-ray crystallography and density functional theory computations.

Recent Advance in Organocatalyzed Asymmetric Reduction of Prochiral Ketones: An Update

Synthesis ◽  
2021 ◽  
Author(s):  
Xu-Long Qin ◽  
Li-Jun Xu ◽  
Fu-She Han
Keyword(s):  
Asymmetric Reduction ◽  
Building Blocks ◽  
Short Review ◽  
Chiral Alcohols ◽  
Comprehensive Overview ◽  
Synthetic Intermediates ◽  
Prochiral Ketones ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions ◽  
Easy Operation

Chiral alcohols are important synthetic intermediates or building blocks for the diverse synthesis of drugs, agrochemicals, and natural products. Asymmetric reduction of prochiral ketones has been the most popularly investigated method for accessing chiral alcohols. In this regard, the organocatalyzed asymmetric reduction as a complementary of transition-metal- and enzyme-catalyzed reactions have attracted tremendous interest in the past decades due to the nature of metal-free and easy operation, as well as, principly, the ease of recovery and reuse of catalysts. Following up a comprehensive overview on organocatalyzed asymmetric reduction of prochiral ketones in early 2018, this short review is intended to summarize the recent progress in this area from the beginning of the year 2018 to the end of Aug. 2021.

Biphasic Reaction Engineering

2001 ◽  
Author(s):  
L. K. Doraiswamy
Keyword(s):  
Organic Solvent ◽  
Aqueous Phase ◽  
Homogeneous Catalysis ◽  
Enzymatic Catalysis ◽  
Immobilized Enzymes ◽  
Organic Reactions ◽  
Biphasic Reaction ◽  
Catalyzed Reactions ◽  
Biphasic Systems ◽  
Enzyme Catalyzed Reactions

The chemical equilibria of many industrially important organic reactions in aqueous solutions are often displaced in the direction of the reactants, leading to very low conversions. Therefore, there is a need for an environmentally friendly strategy that will shift the equilibria toward the products, resulting in enhanced conversions. A particularly effective technique is to add a second phase, appropriately termed biphasing. In general, biphasing is the intentional addition of an immiscible phase to a reaction mixture to increase the yield of the desired product or to facilitate separation of product from (say) catalyst. Much of the effort till recently has been on adding a water-immiscible organic solvent in enzyme-catalyzed organic reactions in the aqueous phase. Although strictly the term biphasing should apply only to soluble catalysts, thus preserving the purity of its definition, in practice it also includes insoluble catalysts such as immobilized enzymes (which would constitute a third phase). Biphasing received an exciting stimulus around 1984 when it was used to overcome the inherent and perhaps the most telling deficiency of homogeneous catalysis. By biphasing with an aqueous phase (unlike in enzymatic catalysis where the biphasing liquid is an organic solvent), the catalyst was fully retained in that phase, whereas the product (and unused reactant) remained in the organic phase. The consequent easy separation of catalyst from product added a new dimension to homogeneous catalysis that gives it a decided edge over its heterogeneous counterpart for many reactions. Yet another dimension to biphasing was added in the last decade when it was found that both phases could be aqueous. This variant of traditional biphasing has many obvious advantages. Although still in its infancy, its enormous potential is not difficult to visualize. The chief advantages and disadvantages of biphasing are listed in Table 18.1. We begin our treatment of biphasing by developing the theoretical foundation for predicting an apparent or effective equilibrium constant for a biphasic reaction. This will be done specifically for enzyme-catalyzed reactions, but it can be extended to straight organic synthesis. Several important aspects of these biphasic systems, such as solvent selection and the role of mass transfer, will be discussed.

scholarly journals One-step catalytic asymmetric synthesis of all-syn deoxypropionate motif from propylene: Total synthesis of (2R,4R,6R,8R)-2,4,6,8-tetramethyldecanoic acid

2016 ◽  
Vol 113 (11) ◽  
pp. 2857-2861 ◽  
Author(s):  
Yusuke Ota ◽  
Toshiki Murayama ◽  
Kyoko Nozaki
Keyword(s):  
Building Blocks ◽  
Single Step ◽  
Enzymatic Reactions ◽  
Stereogenic Centers ◽  
Complex Building ◽  
One Step ◽  
Simple Molecules ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions ◽  
Major Acid

In nature, many complex structures are assembled from simple molecules by a series of tailored enzyme-catalyzed reactions. One representative example is the deoxypropionate motif, an alternately methylated alkyl chain containing multiple stereogenic centers, which is biosynthesized by a series of enzymatic reactions from simple building blocks. In organic synthesis, however, the majority of the reported routes require the syntheses of complex building blocks. Furthermore, multistep reactions with individual purifications are required at each elongation. Here we show the construction of the deoxypropionate structure from propylene in a single step to achieve a three-step synthesis of (2R,4R,6R,8R)-2,4,6,8-tetramethyldecanoic acid, a major acid component of a preen-gland wax of the graylag goose. To realize this strategy, we focused on the coordinative chain transfer polymerization and optimized the reaction condition to afford a stereo-controlled oligomer, which is contrastive to the other synthetic strategies developed to date that require 3–6 steps per unit, with unavoidable byproduct generation. Furthermore, multiple oligomers with different number of deoxypropionate units were isolated from one batch, showing application to the construction of library. Our strategy opens the door for facile synthetic routes toward other natural products that share the deoxypropionate motif.

1,2-Dihaloalkenes in Metal-Catalyzed Reactions

Synthesis ◽  
2018 ◽  
Vol 50 (16) ◽  
pp. 3087-3113 ◽  
Author(s):  
Benoit Daoust ◽  
Nicolas Gilbert ◽  
Paméla Casault ◽  
François Ladouceur ◽  
Simon Ricard
Keyword(s):  
Transition Metal ◽  
Building Blocks ◽  
Facile Synthesis ◽  
Bond Forming ◽  
Bond Forming Reactions ◽  
Transition Metal Catalyzed ◽  
Catalyzed Reactions ◽  
Metal Catalyzed

1,2-Dihaloalkenes readily undergo simultaneous or sequential difunctionalization through transition-metal-catalyzed reactions, which makes them attractive building blocks for complex unsaturated motifs. This review summarizes recent applications of such transformations in C–C and C–heteroatom bond forming processes. The facile synthesis of stereodefined alkene derivatives, as well as aromatic and heteroatomic­ compounds, from 1,2-dihaloalkenes is thus outlined.1 Introduction2 Synthesis of 1,2-Dihaloalkenes3 C–C Bond Forming Reactions4 C–Heteroatom Bond Forming Reactions5 Conclusion

Design of an in vitro biocatalytic cascade for the manufacture of islatravir

Science ◽  
2019 ◽  
Vol 366 (6470) ◽  
pp. 1255-1259 ◽  
Author(s):  
Mark A. Huffman ◽  
Anna Fryszkowska ◽  
Oscar Alvizo ◽  
Margie Borra-Garske ◽  
Kevin R. Campos ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Directed Evolution ◽  
Building Blocks ◽  
Hiv Treatment ◽  
Pharmaceutical Manufacturing ◽  
Enzymatic Reactions ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions

Enzyme-catalyzed reactions have begun to transform pharmaceutical manufacturing, offering levels of selectivity and tunability that can dramatically improve chemical synthesis. Combining enzymatic reactions into multistep biocatalytic cascades brings additional benefits. Cascades avoid the waste generated by purification of intermediates. They also allow reactions to be linked together to overcome an unfavorable equilibrium or avoid the accumulation of unstable or inhibitory intermediates. We report an in vitro biocatalytic cascade synthesis of the investigational HIV treatment islatravir. Five enzymes were engineered through directed evolution to act on non-natural substrates. These were combined with four auxiliary enzymes to construct islatravir from simple building blocks in a three-step biocatalytic cascade. The overall synthesis requires fewer than half the number of steps of the previously reported routes.

A kinetic analysis of coupled sequential enzyme reactions

2018 ◽  
Author(s):  
Justin Eilertsen ◽  
Santiago Schnell
Keyword(s):  
Enzyme Assay ◽  
Sequential Reaction ◽  
Enzyme Reactions ◽  
Indicator Reaction ◽  
Single Substrate ◽  
Complex Sequences ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions ◽  
Single Enzyme

<div>As a case study, we consider a coupled enzyme assay of sequential enzyme reactions obeying the Michaelis--Menten reaction mechanism. The sequential reaction consists of a single-substrate, single-enzyme non-observable reaction followed by another single-substrate, single-enzyme observable reaction (indicator reaction). In this assay, the product of the non-observable reaction becomes the substrate of the indicator reaction. A mathematical analysis of the reaction kinetics is performed, and it is found that after an initial fast transient, the sequential reaction is described by a pair of interacting Michaelis--Menten equations. Timescales that approximate the respective lengths of the indicator and non-observable reactions, as well as conditions for the validity of the Michaelis--Menten equations are derived. The theory can be extended to deal with more complex sequences of enzyme catalyzed reactions.</div>

A kinetic analysis of coupled sequential enzyme reactions

2018 ◽  
Author(s):  
Justin Eilertsen ◽  
Santiago Schnell
Keyword(s):  
Enzyme Assay ◽  
Sequential Reaction ◽  
Enzyme Reactions ◽  
Indicator Reaction ◽  
Single Substrate ◽  
Complex Sequences ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions ◽  
Single Enzyme

<div>As a case study, we consider a coupled enzyme assay of sequential enzyme reactions obeying the Michaelis-Menten reaction mechanism. The sequential reaction consists of a single-substrate, single enzyme non-observable reaction followed by another single-substrate, single enzyme observable reaction (indicator reaction). In this assay, the product of the non-observable reaction becomes the substrate of the indicator reaction. A mathematical analysis of the reaction kinetics is performed, and it is found that after an initial fast transient, the sequential reaction is described by a pair of interacting Michaelis-Menten equations. Timescales that approximate the respective lengths of the indicator and non-observable reactions, as well as conditions for the validity of the Michaelis-Menten equations are derived. The theory can be extended to deal with more complex sequences of enzyme catalyzed reactions.</div>

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.

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.

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