Exploring Border Conditions for Spontaneous Emergence of Chirality in Allylboration of 1,2,3-Triazolic Aldehydes.

A case of spontaneous chirality generation was observed during a synthetic project studying the allylboration of 1,2,3-triazolic aldehydes. Here, we present computational studies supported by experimental findings targeting the elucidation of border conditions required for the observation of spontaneous chirality generation in the reaction of 1-Ar-1-1,2,3-triazole-4-carbaldehydes with triallylborane. Three possible sources of symmetry breaking were found computationally.

The Reduction of Carbonyl Compounds with Dicyclopentylzinc: A New Example of Asymmetric Amplifying Autocatalysis.

A previously unknown reduction of carbonyl compounds with dicyclopentylzinc is reported. Aldehydes react in mild conditions yielding corresponding primary alcohols and cyclopentene. Although cyclohexanone and acetophenone are inert to dicyclopentylzinc, a variety of heterocyclic ketones reacted readily, yielding reasonable to high yields of corresponding secondary alcohols.

The Novel Chiral 2(5)-Furanone Sulfones Possessing Terpene Moiety: Synthesis and Biological Activity.

Over the past decades, 2(5)-furanone derivatives have been extensively studied because of their promising ability to prevent the biofilm formation by various pathogenic bacteria. Here, we report the synthesis of a series of optically active sulfur-containing 2(5)-furanone derivatives and characterize their biological activity. Novel thioethers were obtained by an interaction of stereochemically pure 5-()-menthyloxy- or 5-()-bornyloxy-2(5)-furanones with aromatic thiols under basic conditions.

Antimicrobial and Biofilm-Preventing Activity of l-Borneol Possessing 2(5H)-Furanone Derivative F131 against S. aureus—C. albicans Mixed Cultures.

and are human pathogens that are able to form mixed biofilms on the surface of mucous membranes, implants and catheters. In biofilms, these pathogens have increased resistance to antimicrobials, leading to extreme difficulties in the treatment of mixed infections. The growing frequency of mixed infections caused by and requires either the development of new antimicrobials or the proposal of alternative approaches to increase the efficiency of conventional ones.

Homo- and Heterogeneous Glycoconjugates on the Basis of -Glycans and Human Serum Albumin: Synthesis and Biological Evaluation.

Neoglycoconjugates mimicking natural compounds and possessing a variety of biological functions are very successful tools for researchers to understand the general mechanisms of many biological processes in living organisms. These substances are characterized by high biotolerance and specificity, with low toxicity. Due to the difficult isolation of individual glycoclusters from biological objects, special interest has been directed toward synthetic analogs.

Synthetic prodrug design enables biocatalytic activation in mice to elicit tumor growth suppression.

Considering the intrinsic toxicities of transition metals, their incorporation into drug therapies must operate at minimal amounts while ensuring adequate catalytic activity within complex biological systems. As a way to address this issue, this study investigates the design of synthetic prodrugs that are not only tuned to be harmless, but can be robustly transformed in vivo to reach therapeutically relevant levels. To accomplish this, retrosynthetic prodrug design highlights the potential of naphthylcombretastatin-based prodrugs, which form highly active cytostatic agents via sequential ring-closing metathesis and aromatization.

Disrupting tumor onset and growth via selective cell tagging (SeCT) therapy.

This study presents the early framework of selective cell tagging (SeCT) therapy, which is the concept of preferentially labeling specific cells in vivo with chemical moieties that can elicit a therapeutic response. Using glycosylated artificial metalloenzyme (GArM)-based protein labeling, this study reports two separate functional strategies. In one approach, early tumor onset can be suppressed by tagging cancer cells in living mice with an integrin-blocking cyclic-Arg-Gly-Asp (cRGD) moiety, thereby disrupting cell adhesion onto the extracellular matrix.

A Strategy for Tumor Targeting by Higher-Order Glycan Pattern Recognition: Synthesis and In Vitro and In Vivo Properties of Glycoalbumins Conjugated with Four Different N-Glycan Molecules.

Natural glycoconjugates that form glycocalyx play important roles in various biological processes based on cell surface recognition through pattern recognition mechanisms. This work represents a new synthesis-based screening strategy to efficiently target the cancer cells by higher-order glycan pattern recognition in both cells and intact animals (mice). The use of the very fast, selective, and effective RIKEN click reaction (6π-azaelectrocyclization of unsaturated imines) allows to synthesize and screen various structurally well-defined glycoalbumins containing two and eventually four different N-glycan structures in a very short time.

Bidirectional alterations in antibiotics susceptibility in Staphylococcus aureus-Pseudomonas aeruginosa dual-species biofilm.

In mixed infections, the bacterial susceptibility differs significantly compared to monocultures of bacteria, and generally the concentrations of antibiotics required for the treatment increases drastically. For S. aureus and P.

Increasing Susceptibility of Drug-Resistant to Fluconazole and Terbinafine by 2(5)-Furanone Derivative.

The frequency of mycoses caused by drug-resistant fungal pathogen has increased drastically over the last two decades. The spread of drug-resistant strains, along with the limitations of currently available antifungals, complicates the management of fungal infections, thereby representing great challenges for clinical healthcare. Among various antimicrobial pharmacophores, 2(5)-furanone derivatives have demonstrated antimicrobial, antifungal, and antibiofilm activities.

Facile Access to Optically Active 2,6-Dialkyl-1,5-Diazacyclooctanes.

The chiral substituted 1,5-diazacyclooctane (1,5-DACO) is of considerable importance and has attracted attention from a wide range of fields due to their unique chemical and biological properties. Despite the application potential, further study has not been optimized due to difficulties in their synthetic accessibility. Here, we report that the 1,5-DACO bearing a chiral auxiliary obtained from the formal [4+4] cycloaddition of N-alkyl-α,β-unsaturated imines can be further derivatized by nucleophilic alkylation to give various chiral substituted 1,5-DACO derivatives.

Unraveling the Molecular Mechanism of Selective Antimicrobial Activity of 2(5)-Furanone Derivative against .

causes various infectious diseases, from skin impetigo to life-threatening bacteremia and sepsis, thus appearing an important target for antimicrobial therapeutics. In turn, the rapid development of antibiotic resistance and biofilm formation makes it extremely robust against treatment. Here, we unravel the molecular mechanism of the antimicrobial activity of the recently unveiled consisting of three pharmacophores: chlorinated 2(5)-furanone, sulfone, and -menthol moieties.

Cascade Reaction in Human Live Tissue Allows Clinically Applicable Diagnosis of Breast Cancer Morphology.

Clean operating margins in breast cancer surgery are important for preventing recurrence. However, the current methods for determining margins such as intraoperative frozen section analysis or imprint cytology are not satisfactory since they are time-consuming and cause a burden on the patient and on hospitals with a limited accuracy. A "click-to-sense" probe is developed based on the detection of acrolein, which is a substance released by oxidatively stressed cancer cells and can be visualized under fluorescence microscopy.

Targeting Bacillus cereus cells: increasing efficiency of antimicrobials by the bornylpossessing 2(5Н)-furanone derivative.

Among a variety of antimicrobial compounds, the derivatives of 2(5H)-furanone exhibit different effects on Firmicutes and Proteobacteria. While inhibiting quorum-dependent biofilm formation and virulence factor expression by Gram-negative bacteria through specific interference with the AI-2 signaling pathways, these compounds demonstrate bactericidal effects against Gram-positive bacteria. Here we report that 3,4-dichloro-5(S)-[(1S,2R,4S)-1,7,7-trimethylbicyclo[2.

Expanding the Applicability of the Metal Labeling of Biomolecules by the RIKEN Click Reaction: A Case Study with Gallium-68 Positron Emission Tomography.

Radiolabeled biomolecules with short half-life times are of increasing importance for positron emission tomography (PET) imaging studies. Herein, we demonstrate an improved and generalized method for synthesizing a [radiometal]-unsaturated aldehyde as a lysine-labeling probe that can be easily conjugated into various biomolecules through the RIKEN click reaction. As a case study, Ga-PET imaging of U87MG xenografted mice is demonstrated by using the Ga-DOTA-RGDyK peptide, which is selective to α β integrins.

A viable strategy for screening the effects of glycan heterogeneity on target organ adhesion and biodistribution in live mice.

This work represents the first broad study of testing diverse heterogenous glycoconjugates (7 different glycoalbumins) for their differential in vivo binding (11 different cancer cell types) in both cell- and animal-based studies. As a result, various changes in biodistribution, excretion, and even tumor adhesion were observed.

Antimicrobial Effects of Sulfonyl Derivative of 2(5)-Furanone against Planktonic and Biofilm Associated Methicillin-Resistant and -Susceptible .

The gram-positive opportunistic bacterium is one of the most common causatives of a variety of diseases including skin and skin structure infection or nosocomial catheter-associated infections. The biofilm formation that is an important virulence factor of this microorganism renders the antibiotic therapy ineffective, because biofilm-embedded bacteria exhibit strongly increased tolerance to antimicrobials. Here, we describe a novel 3-chloro-5()-[(1,2,5)-2-isopropyl-5-methylcyclohexyloxy]-4-[4-methylphenylsulfonyl]-2(5)-furanone (), possessing a sulfonyl group and -menthol moiety.

Simple Gd-Neu5NAc complexation results in NMR chemical shift asymmetries of structurally equivalent complex-type N-glycan branches.

In the present Communication, we propose a quite simple but previously overlooked approach for conveniently analyzing, assigning, and extracting sialic acid-containing N-glycan structures using high-resolution NMR spectroscopy without pre-installing metal chelators. Paramagnetic metals, such as Gd, appear to bind to the carboxyl groups of N-acetylneuraminic acid when introduced at room temperature, leading to the measurement of nonequivalent proton and carbon NMR spectral signals among otherwise "identical" glycan branched structures.

Sequential Double "Clicks" toward Structurally Well-Defined Heterogeneous -Glycoclusters: The Importance of Cluster Heterogeneity on Pattern Recognition In Vivo.

are prepared on albumin via a double click procedure. The number of glycan molecules present, in addition to the spatial arrangement of glycans in the heterogeneous glycoclusters, plays an important role in the in vivo kinetics and organ-selective accumulation through glycan pattern recognition mechanisms.

In Vivo Gold Complex Catalysis within Live Mice.

Metal complex catalysis within biological systems is largely limited to cell and bacterial systems. In this work, a glycoalbumin-Au complex was designed and developed that enables organ-specific, localized propargyl ester amidation with nearby proteins within live mice. The targeted reactivity can be imaged through the use of Cy7.

One-Pot Evolution of Ageladine A through a Bio-Inspired Cascade towards Selective Modulators of Neuronal Differentiation.

A bio-inspired cascade reaction has been developed for the construction of the marine natural product ageladine A and a de novo array of its N1-substituted derivatives. This cascade features a 2-aminoimidazole formation that is modeled after an arginine post-translational modification and an aza-electrocyclization. It can be effectively carried out in a one-pot procedure from simple anilines or guanidines, leading to structural analogues of ageladine A that had been otherwise synthetically inaccessible.

Glycan multivalency effects toward albumin enable N-glycan-dependent tumor targeting.

Multivalent interactions play an essential role in molecular recognition in living systems. These effects were employed to target tumor cells using albumin clusters bearing ∼10 molecules of asparagine-linked glycans (N-glycans). Noninvasive near-infrared fluorescence imaging clearly revealed A431 tumors implanted in BALB/cA-nu/nu mice after 1h in an N-glycan structure-dependent manner, thereby demonstrating the efficient use of glycan multivalency effects for tumor targeting in vivo.

Exploring the glycan interaction in vivo: Future prospects of neo-glycoproteins for diagnostics.

Herein the biodistributions and in vivo kinetics of chemically prepared neoglycoproteins are reviewed. Chemical methods can be used to conjugate various mono- and oligosaccharides onto a protein surface. The kinetics and organ-specific accumulation profiles of these glycoconjugates, which are introduced through intravenous injections, have been analyzed using conventional dissection studies as well as noninvasive methods such as single photon emission computed tomography, positron emission tomography and fluorescence imaging.

In vivo imaging of advanced glycation end products (AGEs) of albumin: first observations of significantly reduced clearance and liver deposition properties in mice.

Advanced glycation end products (AGEs) are associated with various diseases, especially during aging and the development of diabetes and uremia. To better understand these biological processes, investigation of the in vivo kinetics of AGEs, i.e.

Visualizing Trimming Dependence of Biodistribution and Kinetics with Homo- and Heterogeneous N-Glycoclusters on Fluorescent Albumin.

A series of N-glycans, each sequentially trimmed from biantennary sialoglycans, were homo- or heterogeneously clustered efficiently on fluorescent albumin using a method that combined strain-promoted alkyne-azide cyclization and 6π-azaelectrocyclization. Noninvasive in vivo kinetics and dissection analysis revealed, for the first time, a glycan-dependent shift from urinary to gall bladder excretion mediated by sequential trimming of non-reducing end sialic acids. N-glycoalbumins that were trimmed further, in particular, GlcNAc- and hybrid biantennary-terminated congeners, were selectively taken up by sinusoidal endothelial and stellate cells in the liver, which are critical for diagnosis and treatment of liver fibrillation.