Enzymatic noncovalent synthesis of peptide assemblies generates multimolecular crowding in cells for biomedical applications

2021 ◽  
Author(s):  
Meihui Yi ◽  
Weiyi Tan ◽  
Jiaqi Guo ◽  
Bing Xu

Enzymatic noncovalent synthesis enables spatiotemporal control of multimolecular crowding in cells, thus offering a unique opportunity for modulating cellular functions. This article introduces some representative enzymes and molecular building blocks...

2020 ◽  
Vol 4 (1) ◽  
pp. 35
Author(s):  
Carolina Amorim ◽  
Peter J. Jervis ◽  
Juliana Andrade ◽  
Paula M. T. Ferreira ◽  
José A. Martins

The self-assembly of nanometric structures from molecular building blocks is an effectiveway to make new functional materials for biological and technological applications. [...]


Author(s):  
Daniel Lambrecht ◽  
Eric Berquist

We present a first principles approach for decomposing molecular linear response properties into orthogonal (additive) plus non-orthogonal/cooperative contributions. This approach enables one to 1) identify the contributions of molecular building blocks like functional groups or monomer units to a given response property and 2) quantify cooperativity between these contributions. In analogy to the self consistent field method for molecular interactions, SCF(MI), we term our approach LR(MI). The theory, implementation and pilot data are described in detail in the manuscript and supporting information.


Polyhedron ◽  
2011 ◽  
Vol 30 (15) ◽  
pp. 2550-2557 ◽  
Author(s):  
Katarzyna Suracka ◽  
Alina Bieńko ◽  
Jerzy Mroziński ◽  
Rafał Kruszyński ◽  
Dariusz Bieńko ◽  
...  

2021 ◽  
Author(s):  
Luuk Kortekaas ◽  
Julian Simke ◽  
Niklas Arndt ◽  
Marcus Böckmann ◽  
Nikos Doltsinis ◽  
...  

Molecular photoswitches play a vital role in the development of responsive materials. These molecular building blocks are particularly attractive when multiple stimuli can be combined to bring about physical changes,...


Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4587
Author(s):  
Fanny d’Orlyé ◽  
Laura Trapiella-Alfonso ◽  
Camille Lescot ◽  
Marie Pinvidic ◽  
Bich-Thuy Doan ◽  
...  

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.


2010 ◽  
Vol 299 (6) ◽  
pp. E879-E886 ◽  
Author(s):  
Yael Riahi ◽  
Guy Cohen ◽  
Ofer Shamni ◽  
Shlomo Sasson

The peroxidation of n-3 and n-6 polyunsaturated fatty acids (PUFAs) and of their hydroperoxy metabolites is a complex process. It is initiated by free oxygen radical-induced abstraction of a hydrogen atom from the lipid molecule followed by a series of nonenzymatic reactions that ultimately generate the reactive aldehyde species 4-hydroxyalkenals. The molecule 4-hydroxy- 2E-hexenal (4-HHE) is generated by peroxidation of n-3 PUFAs, such as linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid. The aldehyde product 4-hydroxy-2 E-nonenal (4-HNE) is the peroxidation product of n-6 PUFAs, such as arachidonic and linoleic acids and their 15-lipoxygenase metabolites, namely 15-hydroperoxyeicosatetraenoic acid (15-HpETE) and 13-hydroperoxyoctadecadienoic acid (13-HpODE). Another reactive peroxidation product is 4-hydroxy-2 E,6 Z-dodecadienal (4-HDDE), which is derived from 12-hydroperoxyeicosatetraenoic acid (12-HpETE), the 12-lipoxygenase metabolite of arachidonic acid. Hydroxyalkenals, notably 4-HNE, have been implicated in various pathophysiological interactions due to their chemical reactivity and the formation of covalent adducts with macromolecules. The progressive accumulation of these adducts alters normal cell functions that can lead to cell death. The lipophilicity of these aldehydes positively correlates to their chemical reactivity. Nonetheless, at low and noncytotoxic concentrations, these molecules may function as signaling molecules in cells. This has been shown mostly for 4-HNE and to some extent for 4-HHE. The capacity of 4-HDDE to generate such “mixed signals” in cells has received less attention. This review addresses the origin and cellular functions of 4-hydroxyalkernals.


2012 ◽  
Vol 90 (2) ◽  
pp. 209-217 ◽  
Author(s):  
Svetlana V. Koltsova ◽  
Olga A. Akimova ◽  
Sergei V. Kotelevtsev ◽  
Ryszard Grygorczyk ◽  
Sergei N. Orlov

In the present work, we compared the outcome of hyperosmotic and isosmotic shrinkage on ion transport and protein phosphorylation in C11-MDCK cells resembling intercalated cells from collecting ducts and in vascular smooth muscle cells (VSMC) from the rat aorta. Hyperosmotic shrinkage was triggered by cell exposure to hypertonic medium, whereas isosmotic shrinkage was evoked by cell transfer from an hypoosmotic to an isosmotic environment. Despite a similar cell volume decrease of 40%–50%, the consequences of hyperosmotic and isosmotic shrinkage on cellular functions were sharply different. In C11-MDCK and VSMC, hyperosmotic shrinkage completely inhibited Na+,K+-ATPase and Na+,Pi cotransport. In contrast, in both types of cells isosmotic shrinkage slightly increased rather than suppressed Na+,K+-ATPase and did not change Na+,Pi cotransport. In C11-MDCK cells, phosphorylation of JNK1/2 and Erk1/2 mitogen-activated protein kinases was augmented in hyperosmotically shrunken cells by ∼7- and 2-fold, respectively, but was not affected in cells subjected to isosmotic shrinkage. These results demonstrate that the data obtained in cells subjected to hyperosmotic shrinkage cannot be considered as sufficient proof implicating cell volume perturbations in the regulation of cellular functions under isosmotic conditions.


2015 ◽  
Vol 03 (01n02) ◽  
pp. 1540004 ◽  
Author(s):  
Xialu Wu ◽  
David J. Young ◽  
T. S. Andy Hor

As molecular synthesis advances, we are beginning to learn control of not only the chemical reactivity (and function) of molecules, but also of their interactions with other molecules. It is this basic idea that has led to the current explosion of supramolecular science and engineering. Parallel to this development, chemists have been actively pursuing the design of very large molecules using basic molecular building blocks. Herein, we review the general development of supramolecular chemistry and particularly of two new branches: supramolecular coordination complexes (SCCs) and metal organic frameworks (MOFs). These two fields are discussed in detail with typical examples to illustrate what is now possible and what challenges lie ahead for tomorrow's molecular artisans.


DYNA ◽  
2018 ◽  
Vol 85 (207) ◽  
pp. 29-35
Author(s):  
Claudia Milena Bedoya-Hincapié ◽  
Elisabeth Restrepo-Parra ◽  
Luis Demetrio López-Carreño

The potential of nanotechnology in the biomedical field has been crucial for contributing to the possibility of efficiently meeting present necessities with novel materials. Over the last few decades, nanostructures with a core/shell structure have attracted significant attention because of the possibility of changing their physical properties by varying their chemistry and geometry. These structures have become relevant in targeted therapy (drug delivery and treatments to complement chemotherapy and radiotherapy), imaging and in the stimulation of cellular functions. Thus in this paper the current development of core/shell nanostructures is reviewed, emphasizing the physical properties of those that have been proposed as potentially having biomedical applications, which are based in a magnetic behavior or in a mixture of magnetic and electric (multiferroic) phenomena.


2014 ◽  
Vol 395 (5) ◽  
pp. 515-528 ◽  
Author(s):  
Benjamin Vollmer ◽  
Wolfram Antonin

Abstract Nuclear pore complexes mediate the transport between the cell nucleoplasm and cytoplasm. These 125 MDa structures are among the largest assemblies found in eukaryotes, built from proteins organized in distinct subcomplexes that act as building blocks during nuclear pore complex biogenesis. In this review, we focus on one of these subcomplexes, the Nup93 complex in metazoa and its yeast counterpart, the Nic96 complex. We discuss its essential function in nuclear pore complex assembly as a linker between the nuclear membrane and the central part of the pore and its various roles in nuclear transport processes and beyond.


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