scholarly journals A Peptidomimetic Fluorescent Probe to Detect the Trypsin β2 Subunit of the Human 20S Proteasome

2020 ◽  
Vol 21 (7) ◽  
pp. 2396
Author(s):  
Magdalena Wysocka ◽  
Anita Romanowska ◽  
Natalia Gruba ◽  
Michalina Michalska ◽  
Artur Giełdoń ◽  
...  
Keyword(s):  
Severe Disease ◽  
Reaction System ◽  
Building Blocks ◽  
Selective Inhibitor ◽  
20S Proteasome ◽  
Aminobenzoic Acid ◽  
Sigmoidal Kinetics ◽  
Linear Signal ◽  
Diaminopropionic Acid ◽  
Proteasome 20S

This work describes the chemical synthesis, combinatorial selection, and enzymatic evaluation of peptidomimetic fluorescent substrates specific for the trypsin-like (β2) subunit of the 20S human proteasome. After deconvolution of a library comprising nearly 6000 compounds composed of peg substituted diaminopropionic acid DAPEG building blocks, the sequence ABZ–Dap(O2(Cbz))–Dap(GO1)–Dap(O2(Cbz))–Arg–ANB–NH2, where ABZ is 2-aminobenzoic acid, and ANB- 5 amino 2- nitro benzoic acid was selected. Its cleavage followed sigmoidal kinetics, characteristic for allosteric enzymes, with Km = 3.22 ± 0.02 μM, kcat = 245 s−1, and kcat/Km = 7.61 × 107 M−1 s−1. This process was practically halted when a selective inhibitor of the β2 subunit of the 20S human proteasome was supplemented to the reaction system. Titration of the substrate resulting in decreased amounts of proteasome 20S produced a linear signal up to 10−11 M. Using this substrate, we detected human proteasome 20S in human urine samples taken from the bladders of cancer patients. This observation could be useful for the noninvasive diagnosis of this severe disease.

scholarly journals Magnetic Assembly Route to Construct Reproducible and Recyclable SERS Substrate

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Bingfang Zou ◽  
Chunyu Niu ◽  
Ming Ma ◽  
Lu Zhao ◽  
Yongqiang Wang
Keyword(s):  
Noble Metal ◽  
Reaction System ◽  
Practical Interest ◽  
Building Blocks ◽  
Detection Sensitivity ◽  
Sers Substrate ◽  
Magnetic Assembly ◽  
Surface Enhanced Raman ◽  
Signal Sensitivity ◽  
Uniform Array

AbstractThe fabrication of a uniform array film through assembly of colloidal building blocks is of practical interest for the integrated individual and collective functions. Here, a magnetic assembly route was put forward to organize monodisperse noble metal microspheres into a uniform array film for surface-enhanced Raman scattering (SERS) application, which demonstrated the integrated signal sensitivity of single noble metal microspheres and reproducibility of their assembled uniform array film. For this purpose, monodisperse multifunctional Fe3O4@SiO2@TiO2@Ag (FOSTA) colloidal microspheres as building blocks were successfully synthesized through a homemade ultrasonic-assisted reaction system. When used in SERS test, these multifunctional microspheres could firstly bind the analyte (R6G) from solution and then assembled into a uniform film under an external magnetic field, which exhibited high SERS detection sensitivity with good reproducibility. In addition, due to the TiO2 interlayer in FOSTA colloidal microspheres, the building blocks could be recycled and self cleaned through photocatalytic degradation of the adsorbed analyte for recycling SERS application.

A Dynamic Route to Structure and Function: Recent Advances in Imine-Based Organic Nanostructured Materials

2013 ◽  
Vol 66 (1) ◽  
pp. 9 ◽  
Author(s):  
Yi Liu ◽  
Zhan-Ting Li
Keyword(s):  
Self Assembly ◽  
Reaction System ◽  
Functional Materials ◽  
Building Blocks ◽  
The Self ◽  
Interlocked Molecules ◽  
Functional Aspects ◽  
Imine Bond ◽  
And Function ◽  
Dynamic Route

The chemistry of imine bond formation from simple aldehyde and amine precursors is among the most powerful dynamic covalent chemistries employed for the construction of discrete molecular objects and extended molecular frameworks. The reversible nature of the C=N bond confers error-checking and proof-reading capabilities in the self-assembly process within a multi-component reaction system. This review highlights recent progress in the self-assembly of complex organic molecular architectures that are enabled by dynamic imine chemistry, including molecular containers with defined geometry and size, mechanically interlocked molecules, and extended frameworks and polymers, from building blocks with preprogrammed steric and electronic information. The functional aspects associated with the nanometer-scale features not only place these dynamically constructed nanostructures at the frontier of materials sciences, but also bring unprecedented opportunities for the discovery of new functional materials.

scholarly journals Total synthesis of aStreptococcus pneumoniaeserotype 12F CPS repeating unit hexasaccharide

2017 ◽  
Vol 13 ◽  
pp. 164-173 ◽  
Author(s):  
Peter H Seeberger ◽  
Claney L Pereira ◽  
Subramanian Govindan
Keyword(s):  
Total Synthesis ◽  
Capsular Polysaccharide ◽  
Severe Disease ◽  
Building Blocks ◽  
Positive Bacterium ◽  
Linear Approach ◽  
Starting Point ◽  
Branching Points ◽  
Glycoconjugate Vaccines ◽  
Sequential Assembly

The Gram-positive bacteriumStreptococcus pneumoniaecauses severe disease globally. Vaccines that preventS. pneumoniaeinfections induce antibodies against epitopes within the bacterial capsular polysaccharide (CPS). A better immunological understanding of the epitopes that protect from bacterial infection requires defined oligosaccharides obtained by total synthesis. The key to the synthesis of theS. pneumoniaeserotype 12F CPS hexasaccharide repeating unit that is not contained in currently used glycoconjugate vaccines is the assembly of the trisaccharide β-D-GalpNAc-(1→4)-[α-D-Glcp-(1→3)]-β-D-ManpNAcA, in which the branching points are equipped with orthogonal protecting groups. A linear approach relying on the sequential assembly of monosaccharide building blocks proved superior to a convergent [3 + 3] strategy that was not successful due to steric constraints. The synthetic hexasaccharide is the starting point for further immunological investigations.

scholarly journals Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

2014 ◽  
Vol 10 ◽  
pp. 2453-2460 ◽  
Author(s):  
Markus Nörrlinger ◽  
Thomas Ziegler
Keyword(s):  
Building Blocks ◽  
Aminobenzoic Acid ◽  
Peptide Coupling

New aromatic glycoconjugate building blocks based on the trifunctional 3-aminomethyl-5-aminobenzoic acid backbone and sugars linked to the backbone by a malonyl moiety were prepared via peptide coupling. The orthogonally protected glycoconjugates, bearing an acetyl-protected glycoside, were converted into their corresponding acids which are suitable building blocks for combinatorial glycopeptide synthesis.

scholarly journals Automated glycan assembly of aS. pneumoniaeserotype 3 CPS antigen

2016 ◽  
Vol 12 ◽  
pp. 1440-1446 ◽  
Author(s):  
Markus W Weishaupt ◽  
Stefan Matthies ◽  
Mattan Hurevich ◽  
Claney L Pereira ◽  
Heung Sik Hahm ◽  
...  
Keyword(s):  
Process Improvement ◽  
Late Stage ◽  
Building Block ◽  
Bacterial Infections ◽  
Capsular Polysaccharide ◽  
Glucuronic Acid ◽  
Severe Disease ◽  
Building Blocks ◽  
Oxidation Step ◽  
Chain Lengths

Vaccines againstS. pneumoniae, one of the most prevalent bacterial infections causing severe disease, rely on isolated capsular polysaccharide (CPS) that are conjugated to proteins. Such isolates contain a heterogeneous oligosaccharide mixture of different chain lengths and frame shifts. Access to defined syntheticS. pneumoniaeCPS structures is desirable. Known syntheses ofS. pneumoniaeserotype 3 CPS rely on a time-consuming and low-yielding late-stage oxidation step, or use disaccharide building blocks which limits variability. Herein, we report the first iterative automated glycan assembly (AGA) of a conjugation-readyS. pneumoniaeserotype 3 CPS trisaccharide. This oligosaccharide was assembled using a novel glucuronic acid building block to circumvent the need for a late-stage oxidation. The introduction of a washing step with the activator prior to each glycosylation cycle greatly increased the yields by neutralizing any residual base from deprotection steps in the synthetic cycle. This process improvement is applicable to AGA of many other oligosaccharides.

scholarly journals Conformational and structural stability of the single molecule and hydrogen bonded clusters of para aminobenzoic acid in the gas and solution phases

CrystEngComm ◽  
2018 ◽  
Vol 20 (46) ◽  
pp. 7543-7555 ◽  
Author(s):  
Ian Rosbottom ◽  
Dimitrios Toroz ◽  
Robert B. Hammond ◽  
Kevin J. Roberts
Keyword(s):  
Hydrogen Bonding ◽  
Ab Initio ◽  
Structural Stability ◽  
Single Molecule ◽  
Building Blocks ◽  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
Aminobenzoic Acid ◽  
Cluster Stability ◽  
Hydrogen Bonded

The structures of α- and β-para aminobenzoic acid are deconstructed into their hydrogen bonding molecular structural building blocks, where they are analysed usingab initioquantum mechanical calculations of their conformation and cluster stability in solution.

Kinetic Resolution of α-Nitrolactones by Catalytic Asymmetric Hydrolysis or Ester–Amide Exchange Reaction

Synlett ◽  
2020 ◽  
Vol 31 (20) ◽  
pp. 2018-2022
Author(s):  
Akira Sakakura ◽  
Ryota Nakao ◽  
Yudai Fujii ◽  
Ichiro Hayakawa ◽  
Haruki Mizoguchi
Keyword(s):  
Exchange Reaction ◽  
Ammonium Salt ◽  
Kinetic Resolution ◽  
Reaction System ◽  
Building Blocks ◽  
Amide Exchange ◽  
Catalytic Asymmetric

Abstract C 1-Symmetric chiral ammonium salt catalysts induced a kinetic resolution of racemic α-nitrolactones through an asymmetric ester–amide exchange reaction. The corresponding amides were obtained with high enantioselectivities and high S (= k fast/k slow) values. This reaction system is a useful approach for obtaining carbocyclic quaternary α-nitroamides as chiral building blocks.

scholarly journals The YΦ Motif Defines the Structure-Activity Relationships of Human 20S Proteasome Activators

2021 ◽  
Author(s):  
Kwadwo A. Opoku-Nsiah ◽  
Andres H. de la Pena ◽  
Sarah K. Williams ◽  
Nikita Chopra ◽  
Andrej Sali ◽  
...  
Keyword(s):  
Sequence Space ◽  
20S Proteasome ◽  
Recognition Sequence ◽  
Structure Activity Relationships ◽  
Gate Opening ◽  
Structure Activity ◽  
Eukaryotic Proteins ◽  
Proteasome 20S

The 20S proteasome (20S) facilitates turnover of most eukaryotic proteins. Substrate entry into the 20S first requires opening of gating loops through binding of HbYX motifs that are present at the C-termini of certain proteasome activators (PAs). The HbYX motif has been predominantly characterized in the archaeal 20S, whereas little is known about the sequence preferences of the human 20S (h20S). Here, we synthesized and screened ∼120 HbYX-like peptides, revealing unexpected differences from the archaeal system and defining the h20S recognition sequence as the Y-F/Y (YΦ) motif. To gain further insight, we created a functional chimera of the optimized sequence, NLSYYT, fused to the model activator, PA26E102A.A cryo-EM structure of PA26E102A-h20S identified key interactions, including non-canonical contacts and gate-opening mechanisms. Finally, we demonstrated that the YΦ sequence preferences are tuned by valency, allowing multivalent PAs to sample greater sequence space. These results expand the model for termini-mediated gating and provide a template for the design of h20S activators.

scholarly journals Stimulus, expectations, desires and response strategies:The building blocks of nonlinear interaction dynamics

2002 ◽  
Vol 7 (3) ◽  
pp. 133-149
Author(s):  
Dimitrios S. Dendrinos
Keyword(s):  
Nonlinear Interaction ◽  
Reaction System ◽  
Building Blocks ◽  
Response Strategy ◽  
Response Strategies ◽  
Interaction Dynamics ◽  
The Past ◽  
System A ◽  
Tit For Tat

Stimulus and response functions, as the fundamental blocks of nonlinear interaction dynamics, are analyzed and modeled here, under a variety of interaction strategies. The backbone of the suggested model is a simple iterative dynamical formulation: the magnitude of a signal sent at present is a function of a relevant signal sent—as well as of a signal received—in the past; in turn, a signal received at present is a function of a signal received—as well as of a signal sent—in the past; namely,Ss(n+1)=fs{Ss(n)Sr(n)}    and   Sr(n+1)=fr{Sr(n)Ss(n)}whereSs/ris the size of a signal sent/received, andnis a point in time.Expectations and desires by senders and receivers of signals are introduced in the analysis. As a result, a basic classification of individuals emerges, that of “dreamers” and “cynics.” Three fundamental response strategies are identified, all plays on a theoretically Newtonian action–reaction system. A pair of individual, as well as community, interaction end-states are the focus of the analysis here; their stability properties, under a tit-for-tat response strategy, are studied and their likelihood to occur is considered.

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