Investigating the Relationship between Network Mechanics and Single-Chain Extension Using Biomimetic Polysaccharide Gels

2012 ◽  
Vol 45 (11) ◽  
pp. 4863-4869 ◽  
Author(s):  
Erich Schuster ◽  
Leif Lundin ◽  
Martin A. K. Williams
Keyword(s):  
Chain Extension ◽  
Single Chain ◽  
The Relationship

scholarly journals Exploration and Modulation of Antibody Fragment Biophysical Properties by Replacing the Framework Region Sequences

Antibodies ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 9
Author(s):  
Thomas Cnudde ◽  
Zineb Lakhrif ◽  
Justine Bourgoin ◽  
Fanny Boursin ◽  
Catherine Horiot ◽  
...  
Keyword(s):  
Antibody Fragment ◽  
Relevant Information ◽  
Amino Acid Sequences ◽  
Single Chain ◽  
Biophysical Properties ◽  
Successful Development ◽  
Chain Fragment ◽  
Single Chain Fragment Variable ◽  
The Relationship ◽  
Framework Region

In order to increase the successful development of recombinant antibodies and fragments, it seems fundamental to enhance their expression and/or biophysical properties, such as the thermal, chemical, and pH stabilities. In this study, we employed a method bases on replacing the antibody framework region sequences, in order to promote more particularly single-chain Fragment variable (scFv) product quality. We provide evidence that mutations of the VH- C-C′ loop might significantly improve the prokaryote production of well-folded and functional fragments with a production yield multiplied by 27 times. Additional mutations are accountable for an increase in the thermal (+19.6 °C) and chemical (+1.9 M) stabilities have also been identified. Furthermore, the hereby-produced fragments have shown to remain stable at a pH of 2.0, which avoids molecule functional and structural impairments during the purification process. Lastly, this study provides relevant information to the understanding of the relationship between the antibodies amino acid sequences and their respective biophysical properties.

scholarly journals Synthesis of Sequence-Controlled Multiblock Single Chain Nanoparticles by a Stepwise Folding–Chain Extension–Folding Process

2016 ◽  
Vol 49 (23) ◽  
pp. 8933-8942 ◽  
Author(s):  
Junliang Zhang ◽  
Guillaume Gody ◽  
Matthias Hartlieb ◽  
Sylvain Catrouillet ◽  
Jonathan Moffat ◽  
...  
Keyword(s):  
Chain Extension ◽  
Single Chain ◽  
Folding Process

scholarly journals Conformation of Flexible and Semiflexible Chains Confined in Nanoposts Array of Various Geometries

Polymers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1064 ◽  
Author(s):  
Zuzana Benková ◽  
Lucia Rišpanová ◽  
Peter Cifra
Keyword(s):  
Structure Factor ◽  
Volume Fraction ◽  
Occupation Number ◽  
Chain Extension ◽  
Coarse Grained ◽  
Square Lattice ◽  
Structural Behavior ◽  
Single Chain ◽  
Flexible Chain ◽  
Two Factors

The conformation and distribution of a flexible and semiflexible chain confined in an array of nanoposts arranged in parallel way in a square-lattice projection of their cross-section was investigated using coarse-grained molecular dynamics simulations. The geometry of the nanopost array was varied at the constant post diameter dp and the ensuing modifications of the chain conformation were compared with the structural behavior of the chain in the series of nanopost arrays with the constant post separation Sp as well as with the constant distance between two adjacent post walls (passage width) wp. The free energy arguments based on an approximation of the array of nanopost to a composite of quasi-channels of diameter dc and quasi-slits of height wp provide semiqualitative explanations for the observed structural behavior of both chains. At constant post separation and passage width, the occupation number displays a monotonic decrease with the increasing geometry ratio dc/wp or volume fraction of posts, while a maximum is observed at constant post diameter. The latter finding is attributed to a relaxed conformation of the chains at small dc/wp ratio, which results from a combination of wide interstitial volumes and wide passage apertures. This maximum is approximately positioned at the same dc/wp value for both flexible and semiflexible chains. The chain expansion from a single interstitial volume into more interstitial volumes also starts at the same value of dc/wp ratio for both chains. The dependence of the axial chain extension on the dc/wp ratio turns out to be controlled by the diameter of the interstitial space and by the number of monomers in the individual interstitial volumes. If these two factors act in the same way on the axial extension of chain fragments in interstitial volumes the monotonic increase of the axial chain extension with the dc/wp in the nanopost arrays is observed. At constant wp, however, these two factors act in opposite way and the axial chain extension plotted against the dc/wp ratio exhibits a maximum. In the case of constant post diameter, the characteristic hump in the single chain structure factor whose position correlates with the post separation is found only in the structure factor of the flexible chain confined in the nanopost array of certain value of Sp. The structure factor of the flexible chain contains more information on the monomer organization and mutual correlations than the structure factor of the semiflexible chain. The stiffer chain confined in the nanopost array is composed of low number of statistical segments important for the presence of respective hierarchical regimes in the structure factor.

scholarly journals STRATEGIC ALIGNMENT IN THE BRAZILIAN AUTOMOTIVE CHAIN

2012 ◽  
Vol 5 (1) ◽  
pp. 16 ◽  
Author(s):  
Ricardo Silveira Martins ◽  
Osmar Vieira De Souza Filho ◽  
Susana Carla Farias Pereira ◽  
Luiz Carlos Di Serio
Keyword(s):  
Supply Chain ◽  
Supply Chains ◽  
Inductive Reasoning ◽  
Strategic Alignment ◽  
Descriptive Study ◽  
Single Chain ◽  
New Model ◽  
Automotive Supply ◽  
The Relationship

The research objective is verifying the strategic alignment of supply practices between automakers and suppliers in the Brazilian automotive supply chains. It makes an exploratory-descriptive study of objectives, using quantitative/qualitative procedures and inductive reasoning. The concept used for analyzing the alignment of practices was based on Vachon et al. (2009). The main conclusion of this study is that suppliers and automakers seem to align their supply strategy, giving support to a desirable situation of single chain project. The subsidiary conclusion is the lack of relationship between intensity of the link and misalignment in these companies. The main contributions are the analysis of the relationship established in tiers that are the furthest removed from the focal companies; identification of practices that support the expansion of a new model of arrangements implemented by automakers in Brazil; and understanding of the processes that companies have adopted in order to manage their supply chains and the implications of these activities for the competitiveness of both the company and the supply chain as a whole.

scholarly journals Elucidating the mechanism of fluorinated extender unit loading for improved production of fluorine-containing polyketides

2017 ◽  
Vol 114 (5) ◽  
pp. E660-E668 ◽  
Author(s):  
Omer Ad ◽  
Benjamin W. Thuronyi ◽  
Michelle C. Y. Chang
Keyword(s):  
Polyketide Synthase ◽  
Acyl Carrier Protein ◽  
Type System ◽  
Large Family ◽  
Product Yield ◽  
Building Blocks ◽  
Chain Extension ◽  
Chain Elongation ◽  
Single Chain ◽  
Extender Unit

Polyketides are a large family of bioactive natural products synthesized by polyketide synthase (PKS) enzyme complexes predominantly from acetate and propionate. Given the structural diversity of compounds produced using these two simple building blocks, there has been longstanding interest in engineering the incorporation of alternative extender units. We have been investigating the mechanism of fluorinated monomer insertion by three of the six different modules of the PKS involved in erythromycin biosynthesis (6-deoxyerythronolide B synthase, DEBS) to begin understanding the contribution of different steps, such as enzyme acylation, transacylation, C–C bond formation, and chain transfer, to the overall selectivity and efficiency of this process. In these studies, we observe that inactivation of acis-acyltransferase (AT) domain to circumvent its native extender unit preference leads concurrently to a change of mechanism in which chain extension with fluorine-substituted extender units switches largely to an acyl carrier protein (ACP)-independent mode. This result suggests that the covalent linkage between the growing polyketide chain and the enzyme is lost in these cases, which would limit efficient chain elongation after insertion of a fluorinated monomer. However, use of a standalonetrans-acting AT to complement modules with catalytically deficient AT domains leads to enzyme acylation with the fluoromalonyl-CoA extender unit. Formation of the canonical ACP-linked intermediate with fluoromalonyl-CoA allows insertion of fluorinated extender units at 43% of the yield of the wild-type system while also amplifying product yield in single chain-extension experiments and enabling multiple chain extensions to form multiply fluorinated products.

MOLECULAR DYNAMICS SIMULATION OF THE ADSORPTION AND DIFFUSION OF A SINGLE POLYDIMETHYLSILOXANE POLYMER CHAIN ON A SILICON (111) SURFACE

2012 ◽  
Vol 11 (04) ◽  
pp. 697-708 ◽  
Author(s):  
DAN MU ◽  
JIAN-QUAN LI ◽  
SONG WANG ◽  
JIAN-FENG WANG
Keyword(s):  
Molecular Dynamics ◽  
Adsorption Energy ◽  
Dynamic Properties ◽  
Relative Dielectric Constant ◽  
Degree Of Polymerization ◽  
Dynamics Simulation ◽  
Single Chain ◽  
Dynamics Simulations ◽  
Chain Lengths ◽  
The Relationship

The adsorption of polydimethylsiloxane (PDMS) single chain with different chain lengths on a silicon (111) surface were studied by molecular dynamics simulations. The relative dielectric constant was selected to be 1 and 78.0 to mimic in vacuum and in solution environment, respectively. The chains were all present as two-dimensional (2D) adsorption conformation on the surface but different conformations and dynamic properties were found in the two absolutely different environments. The relationship between the adsorption energy of the different chain lengths and the degree of polymerization follows a linear function and the average adsorption energy per segment is -0.42 kcal/mol. In addition, the diffusion coefficient (D) of such chains scales with the degree of polymerization (N) as N-3/2.

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