Improved methodologies are provided to synthesize (1R,2S)-2-aminocyclobutane-1-carboxylic acid derivatives and their incorporation into beta-peptides of 2-8 residues bearing different N-protecting groups. The conformational analysis these oligomers has been carried out by using experimental techniques along with theoretical calculations. This study shows that adopt preferentially a strand-type conformation in solution induced the formation intra-residue six-membered hydrogen-bonded rings,...

Determining the conformations accessible to carbohydrate ligands in aqueous solution is important for understanding their biological action. In this work, we evaluate conformational free-energy surfaces of Lewis oligosaccharides explicit solvent using a multidimensional variant swarm-enhanced sampling molecular dynamics (msesMD) method; compare with multi-microsecond unbiased MD simulations, umbrella sampling, and accelerated approaches. For sialyl A tetrasaccharide, msesMD simulations...

Chirality of the monomeric residues controls and determines prevalent folding small oligopeptides (from di- to tetramers) composed 2-aminocyclobutane-1-carboxylic acid (ACBA) derivatives with same or different absolute relative configuration. The cis-form ACBA gives rise two conformers, namely, Z6 Z8, while trans-form manifests uniquely as an H8 structure. By combining these subunits in oligo- polypeptides, their local structural preference remains, thus allowing rational design new short...

A set of meta-substituted 3-arylisoquinolinones have been identified that show substantial cytotoxicity in breast, liver, lung and colon cancer cell lines; these are up to 700-fold more active than the corresponding para analogues. These compounds were initially proposed as inhibitors N-ribosyl dihydronicotinamide (NRH): quinone oxidoreductase 2 (NQO2) but found be inactive against enzyme. Instead, COMPARE analysis suggested 6-fluoro-3-(meta-fluorophenyl)isoquinolin-1(2H)-one (4) could mimic...

An efficient strategy toward the synthesis of large-ring cyclodextrin (CD) analogs alternating α,α′-trehalose disaccharide subunits and pseudoamide segments (cyclotrehalans, CTs), involving a bimolecular macrocyclization reaction as key step, is reported. NMR molecular modeling confirmed that eight ten α-d-glucopyranoside in tetrameric pentameric CT homologues (CT4 CT5, respectively) are magnetically equivalent, γ εCD counterparts. Yet, orientation monosaccharide constituents reversed CTs...

Polyaromatic carbon is widely held to be strongly diamagnetic and hydrophobic, with textbook van der Waals 'π-stacked' binding of hydrocarbons, which disrupt their self-assembled supramolecular structures. The NMR organic molecules sequestered by polyaromatic expected dominated shielding from the orbital diamagnetism π electrons. We report first evidence very different polar magnetic behavior in water, wherein graphene remained well-dispersed after extensive dialysis behaved as a...

Traditional therapeutic interventions against abnormal gene expression in disease states at the level of expressed proteins are becoming increasingly difficult due to poor selectivity, off-target effects and associated toxicity. Upstream catalytic targeting specific RNA sequences offers an alternative platform for drug discovery achieve more potent selective treatment through antisense interference with disease-relevant RNAs. We report a novel class biomaterials, comprising amphipathic...

Protein plasticity, while often linked to biological function, also provides opportunities for rational design of selective and potent inhibitors their function. The application computational methods the prediction concealed protein concavities is challenging, as motions involved can be significant occur over long time scales. Here we introduce swarm-enhanced sampling molecular dynamics (sesMD) method a tool improve conformational landscapes. In this approach, swarm replica simulations...

Drug repositioning offers an effective alternative to de novo drug design tackle the urgent need for novel antimalarial treatments. The antiamoebic compound emetine dihydrochloride has been identified as a potent in vitro inhibitor of multidrug-resistant strain K1 Plasmodium falciparum (50% inhibitory concentration [IC 50 ], 47 nM ± 2.1 [mean standard deviation]). Dehydroemetine, synthetic analogue dihydrochloride, reported have less-cardiotoxic effects than emetine.

Abstract Free energy simulations are an established computational tool in modelling chemical change the condensed phase. However, sampling of kinetically distinct substates remains a challenge to these approaches. As route addressing this, we link methods thermodynamic integration (TI) and swarm‐enhanced molecular dynamics (sesMD), where simulation replicas interact cooperatively aid transitions over barriers. We illustrate approach by using alchemical alkane transformations solution,...

A series of new chiral molecular tweezers, di-(R,R)-1-[10-(1-hydroxy-2,2,2-trifluoroethyl)-9-anthryl]-2,2,2-trifluoroethyl phthalate (2), isophthalate (3) and terephthalate (4), were synthesized their structure studied by NMR mechanics. Their effectiveness as solvating agents for the determination enantiomeric purity compounds using was demonstrated.

Potent knockdown of pathogenic RNA in vivo is an urgent health need unmet by both small-molecule and biologic drugs. 'Smart' supramolecular assembly catalysts offers precise recognition potent destruction targeted RNA, hitherto not found nature. Peptidyl-oligonucleotide ribonucleases are here chemically engineered to create attack bulge-loop regions upon hybridization target RNA. Catalytic peptide was incorporated either via a centrally modified nucleotide (Type 1) or through abasic sugar...

The configurational and conformational structure of alfentanil hydrochloride (1) was studied by nuclear magnetic resonance theoretical calculations. Compound 1 is best described equilibrium between two stereoisomeric piperidinium rings with the N-substituent always being in equatorial position. Nuclear spectra demonstrate that, depending on solvent, adopts conformation an axial methoxymethylene group. Computations were crucial determining importance transannular attractive interaction...

<p>Determining the conformations accessible to carbohydrate ligands in aqueous solution is important for understanding their biological action. In this work, we evaluate conformational free energy surfaces of Lewis oligosaccharides explicit solvent using a multidimensional variant swarm-enhanced sampling molecular dynamics (msesMD) method; compare with multi-microsecond unbiased MD simulations, umbrella and accelerated approaches. For sialyl A tetrasaccharide, msesMD simulations...

A structural and energetic study on three types of cyclodextrinic carcerands formed by linking two units α-, β-, or γ-cyclodextrin through methylene chains several lengths was performed molecular mechanics, dynamics simulations.The smaller are rigid spherical, while the larger more flexible, their cavities hidden, they spheroidal.The small having one bridge per glucose present "laevo", symmetrical, "dextro" arrangements due to formation hydrogen bonds between CD units, those with bridges...

Abstract There is an increasing demand on the market for environmentally compatible lubricants. Refined vegetable oils have been used as biolubricants, but synthetic esters from renewable resources could also be considered and can prepared by combining different alcohols with linear or branched fatty acids. A tool has developed to predict properties of based chemical structure. multilinear approach was correlate experimental viscosity theoretical parameters (diffusion coefficient, dipole...

Determining the conformations accessible to carbohydrate ligands in aqueous solution is important for understanding their biological action. In this work, we evaluate conformational free energy surfaces of Lewis oligosaccharides explicit solvent using a multidimensional variant swarm-enhanced sampling molecular dynamics (msesMD) method; compare with multi-microsecond unbiased MD simulations, umbrella and accelerated approaches. For sialyl A tetrasaccharide, msesMD simulations predict...

Abstract Drug repositioning offers an effective alternative to de novo drug design tackle the urgent need for novel anti-malarial treatments. The anti-amoebic compound, emetine dihydrochloride, has been identified as a potent in-vitro inhibitor of multi-drug resistant strain K1 Plasmodium falciparum (IC 50 : 47 nM + 2.1 nM). 2,3-dehydroemetine, synthetic analogue dihydrochloride claimed have less cardiotoxic effects than emetine. structures two diastereoisomers 2,3-dehydroemetine were...