Abstract Recently, functional connections between S-adenosylhomocysteine hydrolase (AHCY) activity and cancer have been reported. As the properties of AHCY include hydrolysis maintenance cellular methylation potential, connection is not obvious. The mechanisms by which influences cell cycle or proliferation yet confirmed. To elucidate AHCY-driven cancer-specific mechanisms, we pursued a multi-omics approach to investigate effect AHCY-knockdown on hepatocellular carcinoma cells. Here, show...

Bioconjugate bidentate ligands 2–10 were obtained by tethering triphenylphosphanecarboxylic acid to amino substituted spacers with different flexibility, ranging from a rigid enediyne-based β-turn inducer flexible linear aliphatic chains up eight carbon atoms. The 21 synthesized revealed 81% ee selectivity in rhodium-catalyzed asymmetric hydrogenation of α,β-unsaturated acids. key feature the catalysts is prochiral coordination sphere catalytic metal while chirality transmitted "backdoor...

Abstract Owing to the diversity of carbohydrate structures and their significance for function many biopolymers, structural analysis various carbohydrate‐related compounds is great importance. Electrospray ionization tandem mass spectrometry (ESI‐MS/MS) was used establish fragmentation behaviour a range sugar–peptide adducts as model widespread glycoprotein structures. The in this study were chosen provide correlation distinct fragment ions with specific differences, namely position type...

We describe the utilization of bis-isopropylidene-protected d-fructose-derived aldehyde in Passerini reaction with various acids and isocyanides. A library densely functionalized glycomimetics bearing up to 3 carbohydrate units was obtained high yields diastereoselectivities. The configuration newly formed stereocenter determined diastereoselectivity rationalized by DFT calculations.

The γ-lactam motif is often found in naturally occurring compounds with diverse biological activities. We prepared a 28-member library of N-substituted γ-lactams following single-pot, three-component Ugi reaction comprising bifunctional building block, l-glutamic acid methyl ester. tolerates structurally carbonyl and isocyanide components providing robust access to functionalized γ-lactams. Antimicrobial susceptibility testing, including agar well diffusion assay, serial microdilution broth...

Enediyne−peptide conjugates are recently recognized as useful tools in targeting various proteins, while the mechanism underlying observed activity remains somewhat unclear. Addressing these issues, we have prepared acyclic amino acid derived enediynes and disclosed a novel thermally induced cyclization−elimination pathway. Initial formation of 1,4-benzene diradical H-atom abstraction from an external donor is followed by SN2 substitution leading to 2,3-dihydrobenzo[f]isoindoles. The...

Abstract Nonenzymatic protein glycation is caused by a Schiff's base reaction between the aldehyde groups of reducing sugars and primary amines proteins. These structures may undergo further Amadori rearrangement free radical‐mediated oxidation to finally generate irreversible advanced end products (AGEs). One factors known modulate proteins glutathione, most abundant nonprotein thiol tripeptide with γ‐linkage, H‐Glu(Cys‐Gly‐OH)‐OH (GSH). Screening for formed GSH D ‐glucose an essential step...

Metabolic profiling of biological samples involves nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry coupled with powerful statistical tools for complex data analysis. Here, we report a robust, sparseness-based method the blind separation analytes from mixtures recorded in spectroscopic spectrometric measurements. The advantage proposed comparison to alternative decomposition schemes is that it capable estimating number analytes, their concentrations, themselves available...

Underdetermined blind separation of nonnegative dependent sources consists in decomposing a set observed mixed signals into greater number original and component (source) signals. That is an important problem for which very few algorithms exist. It also practically relevant contemporary metabolic profiling biological samples, such as biomarker identification studies, where (a.k.a. pure components or analytes) are aimed to be extracted from mass spectra complex multicomponent mixtures. This...

The kinetics of scalenohedral calcite crystal growth in the presence N-salicyloil-l-aspartic (N-Sal-Asp) and N-salicyloil-l-glutamic acid (N-Sal-Glu), as selected models anti-inflammatory drug-like substances, were analyzed order to study molecular interactions salicylates with {2 1 4} surfaces. results revealed that is controlled by surface reactions, proceeding at spiral step. additives caused inhibition growth, wherein N-Sal-Asp interacted more strongly than N-Sal-Glu. obtained data...

We report the synthesis of a structurally diverse library chiral Nβ-substituted 1,2-diazetidin-3-ones by 4-center 3-component Ugi reaction comprising unprotected α-hydrazino acids. Various isocyanides and carbonyl compounds both aldehydes ketones were utilized. In addition, postcondensation modifications at three different sites have been demonstrated.

Abstract The paper presents sparse component analysis (SCA)‐based blind decomposition of the mixtures mass spectra into pure components, wherein number is less than components. Standard solutions related source separation (BSS) problem that are published in open literature require to be greater or equal unknown Specifically, we have demonstrated experimentally capability SCA blindly extract five components from two only. Two approaches tested: first one based on ℓ 1 norm minimization...

Predicting antitumor activity of compounds using regression models trained on a small number with measured biological is an ill-posed inverse problem. Yet, it occurs very often within the academic community. To counteract, up to some extent, overfitting problems caused by training data, we propose use consensus six for prediction virtual library compounds. The QSAR descriptors 22 related opioid growth factor (OGF, Tyr-Gly-Gly-Phe-Met) known were used train models: feed-forward artificial...

A series of novel hydrazino-based peptidomimetics and analogues comprising N-terminal lysine C-terminal phenanthridinyl-l-alanine were prepared. The presented results demonstrate the up to now unknown possibility finely modulate peptide interactions with DNA/RNA by α-hydrazino group insertion how different positioning two groups in peptides controls binding various double stranded single DNA RNA. All bind 1-10 micromolar affinity ds-DNA/RNA, whereby mode is a combination electrostatic...

We applied a multicomponent approach to access library of densely functionalized homo- and hetero-multivalent glycomimetics comprising aldehyde, amine, isocyanide components related isopropylidene-protected d-fructose, l-sorbose, d-galactose, d-allose. Passerini products were obtained in very good yields (up 78%) high diastereoselectivities 98:2). Three types by the Ugi reaction; along with "classical" four-component product, α-acylaminoamides, three-component α-aminoamides, four- component...

Carbohydrate−peptide conjugates in which D-glucose is linked through an ester linkage to the carboxy group of Tyr-Pro (2), Tyr-Pro-Phe (5) or Tyr-Pro-Phe-Val (11), C6 hydroxy sugar moiety were synthesized examine utility this type monosaccharide modification for peptide prodrugs. Evidence provided that glycoconjugates 2, 5, and 11 easily undergo intramolecular chemical transformations, subsequent attack free N-terminal amino at backbone anomeric position moiety, resulting formation...

Peptidomimetics based on hydrazino derivatives of α-amino acids represent an important class peptidic foldamers with promising biological activities, like protease inhibition and antimicrobial activity. However, the lack straightforward method for synthesis optically pure efficient incorporation building blocks into peptide sequence hamper wider exploitation peptidomimetics. Here we described utility N α-benzyl protected unprotected natural in While α-benzyl-hydrazino chain deprotection...