Monoclonal antibody proteomics: discovery and prevalidation of chronic obstructive pulmonary disease biomarkers in a single step

We define mAb proteomics as the global generation of disease specific antibodies that permit mass screening of biomarkers. An integrated, high-throughput, disease-specific mAb-based biomarker discovery platform has been developed. The approach readily provided new biomarker leads with the focus on large-scale discovery and production of mAb-based, disease-specific clinical assay candidates. The outcome of the biomarker discovery process was a highly specific and sensitive assay, applicable for testing of clinical validation paradigms, like response to treatment or correlation with other clinical parameters. In contrast to MS-based or systems biology-based strategies, our process produced prevalidated clinical assays as the outcome of the discovery process. By re-engineering the biomarker discovery paradigm, the encouraging results presented in this paper clearly demonstrate the efficiency of the mAb proteomics approach, and set the grounds for the next steps of studies, namely, the hunt for candidate biomarkers that respond to drug treatment.     

A compehensive study of $${\vavec{}}$$-Dowling polynomials

After his extensive study of Whitney numbers, Benoumhani introduced Dowling numbers and polynomials as generalizations of the well-known Bell numbers and polynomials. Later, Cheon and Jung gave the r-generalization of these notions. Based on our recent combinatorial interpretation of r-Whitney numbers, in this paper we derive several new properties of r-Dowling polynomials and we present alternative proofs of some previously known ones.     

Factors Affecting Synthetic Dye Adsorption; Desorption Studies: A Review of Results from the Last Five Years (2017–2021)

The primary, most obvious parameter indicating water quality is the color of the water. Not only can it be aesthetically disturbing, but it can also be an indicator of contamination. Clean, high-quality water is a valuable, essential asset. Of the available technologies for removing dyes, adsorption is the most used method due to its ease of use, cost-effectiveness, and high efficiency. The adsorption process is influenced by several parameters, which are the basis of all laboratories researching the optimum conditions. The main objective of this review is to provide up-to-date information on the most studied influencing factors. The effects of initial dye concentration, pH, adsorbent dosage, particle size and temperature are illustrated through examples from the last five years (2017–2021) of research. Moreover, general trends are drawn based on these findings. The removal time ranged from 5 min to 36 h (E = 100% was achieved within 5–60 min). In addition, nearly 80% efficiency can be achieved with just 0.05 g of adsorbent. It is important to reduce adsorbent particle size (with Φ decrease E = 8–99%). Among the dyes analyzed in this paper, Methylene Blue, Congo Red, Malachite Green, Crystal Violet were the most frequently studied. Our conclusions are based on previously published literature.     

A mainly NMR-based structure elucidation of a surprising vindoline trimer with the aid of non-uniform sampled 1H-13C HSQC and HMBC spectra

Structural Chemistry - Two unexpected and unusual vindoline trimers, a ketone and a methyl ether cation, were isolated from a reaction aimed at producing new, synthetically modified vinca...     

A theoretical case study of type I and type II beta-turns

NMR chemical shielding anisotropy tensors have been computed by employing a medium size basis set and the GIAO-DFT(B3LYP) formalism of electronic structure theory for all of the atoms of type I and type II beta-turn models. The models contain all possible combinations of the amino acid residues Gly, Ala, Val, and Ser, with all possible side-chain orientations where applicable in a dipeptide. The several hundred structures investigated contain either constrained or optimized phi, psi, and chi dihedral angles. A statistical analysis of the resulting large database was performed and multidimensional (2D and 3D) chemical-shift/chemical-shift plots were generated. The (1)H(alpha-13)C(alpha), (13)C(alpha-1)H(alpha-13)C(beta), and (13)C(alpha-1)H(alpha-13)C' 2D and 3D plots have the notable feature that the conformers clearly cluster in distinct regions. This allows straightforward identification of the backbone and side-chain conformations of the residues forming beta-turns. Chemical shift calculations on larger For-(L-Ala)(n)-NH(2) (n=4, 6, 8) models, containing a single type I or type II beta-turn, prove that the simple models employed are adequate. A limited number of chemical shift calculations performed at the highly correlated CCSD(T) level prove the adequacy of the computational method chosen. For all nuclei, statistically averaged theoretical and experimental shifts taken from the BioMagnetic Resonance Bank (BMRB) exhibit good correlation. These results confirm and extend our previous findings that chemical shift information from selected multiple-pulse NMR experiments could be employed directly to extract folding information for polypeptides and proteins.     

C8-selective biomimetic transformation of 5,7-dihydroxylated flavonoids by an acid-catalysed phenolic Mannich reaction: Synthesis of flavonoid alkaloids with quercetin and (–)-epicatechin skeletons

We hereby report the biomimetic synthesis of three flavonoid alkaloids, namely 8-(2″-pyrrolidinon-5″-yl)quercetin, 6-(2″-pyrrolidinon-5″-yl)-(–)-epicatechin and 8-(2″-pyrrolidinon-5″-yl)-(–)-epicatechin. These known natural products were prepared via an acid-catalysed regioselective phenolic Mannich reaction involving the electrophilic attack of an N-acyliminium ion on the corresponding flavonoidal precursors. The products were purified by preparative HPLC. The reactions showed high C8-regioselectivity. The major isomers of the synthesized flavonoid alkaloids were further characterized in terms of their medicinal-chemical properties.     

Synthesis of asymmetrically substituted cyclen-based ligands for the controlled sensitisation of lanthanides

A series of unsymmetrical cyclen-based ligands incorporating an antenna and a quencher have been prepared for the complexation of the visible- (Eu, Tb) and near IR-emitting (Nd, Yb) lanthanides. Eu and Tb were sensitised with coumarin 2, and Nd and Yb with rhodamine. Both antennae were paired with nucleoside (uridine and adenosine) quenchers. The interaction between the quencher and the antenna can be regulated by the addition of the complementary base or DNA to the complexes, resulting in changes in the lanthanide luminescence intensity and lifetime.     

A combined electronegativity equalization and electrostatic potential fit method for the determination of atomic point charges

We report an approach for the determination of atomic monopoles of macromolecular systems using connectivity and geometry parameters alone. The method is appropriate also for the calculation of charge distributions based on the quantum mechanically determined wave function and does not suffer from the mathematical instability of other electrostatic potential fit methods.     

Peptide epitope-imprinted polymer microarrays for selective protein recognition. Application for SARS-CoV-2 RBD protein

We introduce a practically generic approach for the generation of epitope-imprinted polymer-based microarrays for protein recognition on surface plasmon resonance imaging (SPRi) chips. The SPRi platform allows the subsequent rapid screening of target binding kinetics in a multiplexed and label-free manner. The versatility of such microarrays, both as synthetic and screening platform, is demonstrated through developing highly affine molecularly imprinted polymers (MIPs) for the recognition of the receptor binding domain (RBD) of SARS-CoV-2 spike protein. A characteristic nonapeptide GFNCYFPLQ from the RBD and other control peptides were microspotted onto gold SPRi chips followed by the electrosynthesis of a polyscopoletin nanofilm to generate in one step MIP arrays. A single chip screening of essential synthesis parameters, including the surface density of the template peptide and its sequence led to MIPs with dissociation constants (K_D) in the lower nanomolar range for RBD, which exceeds the affinity of RBD for its natural target, angiotensin-convertase 2 enzyme. Remarkably, the same MIPs bound SARS-CoV-2 virus like particles with even higher affinity along with excellent discrimination of influenza A (H3N2) virus. While MIPs prepared with a truncated heptapeptide template GFNCYFP showed only a slightly decreased affinity for RBD, a single mismatch in the amino acid sequence of the template, i.e. the substitution of the central cysteine with a serine, fully suppressed the RBD binding.

We introduce highly affine epitope-imprinted polymer-based microarrays for selective protein detection by surface plasmon resonance imaging as shown through the selective recognition of the receptor binding domain of SARS-CoV-2 spike protein.