Peptoids as tools and sensors.

A review of molecular tools and sensors assembled on N-substituted glycine, or α-peptoid, oligomers between 2013 and November 2018 with the following sections: (a) Peptoids as crystal growth modifiers, (b) Peptoids as catalysts, (c) Ion and molecule sequestration and transport, (d) Peptoid sensors, (e) Macromolecule recognition, (f) Cellular transporters, (g) Medical imaging, (h) Future direction and (i) Summary and outlook. Peptoids are a promising class of peptide mimic making them an excellent platform for functional molecule preparation. Attributes of peptoid oligomers include: (a) the ease of precise sequence definition and mono-dispersity; (b) access to a vast chemical space within simple and repeating chemical preparative steps and (c) thermal, chemical and biological stability all lending support for their application in a number of areas, with some that have been realised to date.

Applied metabolomics in drug discovery.

Introduction: The metabolic profile is a direct signature of phenotype and biochemical activity following any perturbation. Metabolites are small molecules present in a biological system including natural products as well as drugs and their metabolism by-products depending on the biological system studied. Metabolomics can provide activity information about possible novel drugs and drug scaffolds, indicate interesting targets for drug development and suggest binding partners of compounds.

A spectroscopic study of substituted anthranilic acids as sensitive environmental probes for detecting cancer cells.

Small-molecule fluorescent reporters of disease states are highly sought after, yet they remain elusive. Anthranilic acids are extremely sensitive environmental probes, and hold promise as general but selective agents for cancer-cell detection if they can be equipped with the appropriate targeting groups. The optical properties of a small library of N-isopropyl invariant anthranilic acids were investigated in methanol and chloroform.

Metal-Free, Acid-Catalyzed ortho-Directed Synthesis of Anthranilic Acid Derivatives Using Carbodiimides.

One-pot syntheses of fluorescent o-aminobenzoates, o-aminopyridine carboxylates, and a 2'-amino-[1,1'-biphenyl]-2-carboxylic acid are described. Carbodiimides are used as the source of the 2-amino function which inserts onto an aromatic ring using S(N)Ar reaction conditions. This method proceeds regiospecifically with a range of 2-fluoroaromatic acids or esters bearing further aryl fluorine, trifluoromethyl, and cyano substituents.

Metabolic Effects of Known and Novel HDAC and SIRT Inhibitors in Glioblastomas Independently or Combined with Temozolomide.

Inhibition of protein deacetylation enzymes, alone or in combination with standard chemotherapies, is an exciting addition to cancer therapy. We have investigated the effect of deacetylase inhibition on the metabolism of glioblastoma cells. 1H NMR metabolomics analysis was used to determine the major metabolic changes following treatment of two distinct glioblastoma cell lines, U373 and LN229, with five different histone deacetylase (HDAC) inhibitors, as well as one inhibitor of NAD+-dependent protein deacetylases (SIRT).

Small head-to-tail macrocyclic α-peptoids.

A convenient and efficient methodology for the head-to-tail macrocyclization of small 3-mer, 4-mer, and 5-mer α-peptoid acids (9-, 12-, and 15-atom N-substituted glycine oligomers) is described. The cyclic trimer has a ccc amide sequence in the crystal structure, whereas the tetramer has ctct and the pentamer has ttccc stereochemistry. NMR analysis reveals rigid structures in solution.

¹H NMR metabolomics analysis of the effect of dichloroacetate and allopurinol on breast cancers.

Metabolomics analysis was used to determine the effect of two well known, non-proprietary metabolic modulators, dichloroacetate and allopurinol on breast cancer cell lines. Dichloroacetate, a pyruvate dehydrogenase kinase inhibitor and allopurinol, a xanthine oxidase/dehydrogenase inhibitor, have been previously explored as chemotherapeutics showing potential in some cancer subtypes while at the same time leading to unexpected increase in proliferation in others. In this work, metabolic effects of these drugs, applied singly and in combination, were explored in three different breast cell lines including cancer cells, MDA-MB-231 and MCF-7 and normal control cell line, MCF-10A.

Targeting the latest hallmark of cancer: another attempt at 'magic bullet' drugs targeting cancers' metabolic phenotype.

The metabolism of tumors is remarkably different from the metabolism of corresponding normal cells and tissues. Metabolic alterations are initiated by oncogenes and are required for malignant transformation, allowing cancer cells to resist some cell death signals while producing energy and fulfilling their biosynthetic needs with limiting resources. The distinct metabolic phenotype of cancers provides an interesting avenue for treatment, potentially with minimal side effects.

1H NMR metabolomics analysis of glioblastoma subtypes: correlation between metabolomics and gene expression characteristics.

Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by unpredictable clinical behaviors that suggest distinct molecular subtypes. With the tumor metabolic phenotype being one of the hallmarks of cancer, we have set upon to investigate whether GBMs show differences in their metabolic profiles. (1)H NMR analysis was performed on metabolite extracts from a selection of nine glioblastoma cell lines.

MetaboHunter: an automatic approach for identification of metabolites from 1H-NMR spectra of complex mixtures.

Background: One-dimensional 1H-NMR spectroscopy is widely used for high-throughput characterization of metabolites in complex biological mixtures. However, the accurate identification of individual compounds is still a challenging task, particularly in spectral regions with higher peak densities. The need for automatic tools to facilitate and further improve the accuracy of such tasks, while using increasingly larger reference spectral libraries becomes a priority of current metabolomics research.

Development and experimental validation of a 20K Atlantic cod (Gadus morhua) oligonucleotide microarray based on a collection of over 150,000 ESTs.

The collapse of Atlantic cod (Gadus morhua) wild populations strongly impacted the Atlantic cod fishery and led to the development of cod aquaculture. In order to improve aquaculture and broodstock quality, we need to gain knowledge of genes and pathways involved in Atlantic cod responses to pathogens and other stressors. The Atlantic Cod Genomics and Broodstock Development Project has generated over 150,000 expressed sequence tags from 42 cDNA libraries representing various tissues, developmental stages, and stimuli.

Solid-phase synthesis of N-substituted glycine oligomers (alpha-peptoids) and derivatives.

Peptoids (N-substituted polyglycines and extended peptoids with variant backbone amino-acid monomer units) are oligomeric synthetic polymers that are becoming a valuable molecular tool in the biosciences. Of particular interest are their applications to the exploration of peptoid secondary structures and drug design. Major advantages of peptoids as research and pharmaceutical tools include the ease and economy of synthesis, highly variable backbone and side-chain chemistry possibilities.

Cell culture metabolomics: applications and future directions.

Metabolomics represents a global quantitative assessment of metabolites within a biological system. The metabolic analysis of cell cultures has many potential applications and advantages to currently used methods for cell line testing. Metabolite concentrations represent sensitive markers of both genomic and phenotypic changes.

NMR metabolic analysis of samples using fuzzy K-means clustering.

The global analysis of metabolites can be used to define the phenotypes of cells, tissues or organisms. Classifying groups of samples based on their metabolic profile is one of the main topics of metabolomics research. Crisp clustering methods assign each feature to one cluster, thereby omitting information about the multiplicity of sample subtypes.

Chemical exchange in novel spirobicyclic zwitterionic Janovsky complexes using dynamic 1H NMR spectroscopy.

Highly coloured Janovsky complexes have been known for over 120 years, being used in many colourimetric analytical procedures. In this present study, two novel and stable nitrocyclohexadienyl spirobicyclic, zwitterionic Janovsky anionic hydantoin sigma-complexes, rac-1,3-diisopropyl-6-nitro-2,4-dioxo-1,3-diazaspiro[4.5]deca-6,9-dien-8-ylideneazinate, ammonium internal salt (1) and 1,3-diisopropyl-2,4-dioxo-1,3-diazaspiro[4.

Integrated analysis of transcriptomics and metabolomics profiles.

Background: Integrated analysis of transcriptomics and metabolomics data has the potential greatly to increase our understanding of metabolic networks and biological systems leading to various potential clinical applications.

Objective: The aim is to present different applications as well as analysis tools utilized for the parallel study of gene and metabolite expressions.

Methods: Publications dealing with integrated analysis of gene and metabolite expression data as well as publications describing tools that can be used for integrated analysis are reviewed.

Fast deprotection of synthetic oligodeoxyribonucleotides using standard reagents under microwave irradiation.

Fast methods for the removal of permanent amide exo-cyclic protective groups widely used in phosphoramidite-method DNA synthesis are desirable for many genomics and proteomics applications. In this communication, we present a method for the deprotection of a range of N-acyl deoxyribonucleosides (T, dA Bz, dC Bz, dC Ac, dG ibu, dG PAC) and synthetic oligodeoxyribonucleotides, ranging in length from 5-mer to 50-mer. Oligodeoxyribonucleotides were synthesized using standard amide protecting groups (dA Bz, dC Bz, dG ibu) and phosphoramidite chemistry on cis-diol solid phase support.

Microarray analysis of alternative splicing.

Alternative splicing, defined as the generation of multiple RNA transcript species from a common mRNA precursor, is one of the mechanisms for the diversification and expansion of cellular proteins from a smaller set of genes. Current estimates indicate that at least 60% of genes in the human genome exhibit alternative splicing. Over the past decade, alternative splicing has increasingly been recognized as a major regulatory process with a critical role in normal development.

Carbohydrate microarrays: survey of fabrication techniques.

Carbohydrate microarrays are being developed in order to decipher the information content of the glycome. This postgenomic activity is necessary because of the complexity of protein biosynthesis and post-translational modifications that cannot currently be detected at the genome level. This review looks, in detail, at the experimental approaches that have been taken in the fabrication and preparation of carbohydrate microarrays, glycan arrays and glyco-chips.

Data analysis of alternative splicing microarrays.

The importance of alternative splicing in drug and biomarker discovery is best understood through several example genes. For most genes, the identification, detection and particularly quantification of isoforms in different tissues and conditions remain to be carried out. As a result, the focus in drug and biomarker development is increasingly on high-throughput studies of alternative splicing.

Tritium NMR studies of the human carbonic anhydrase I-benzenesulfonamide complex.

Tritium NMR spectroscopy has been used to examine the complex formed by [4-3H]benzenesulfon-amide and human carbonic anhydrase I. The results show that in solution the inhibitor forms a 1:1 complex with the enzyme. A 100-spin computational model of the system, constructed with reference to crystallographic results, was used to interpret tritium relaxation behavior and 3H{1H} NOEs.

Applications of tritium NMR to macromolecules: a study of two nucleic acid molecules.

We have tritium labeled two nucleic acid molecules, an 8 kDa DNA oligomer and a 20 kDa 'hammer-head' RNA for tritium NMR investigations. The DNA sequence studied has been previously used in homonuclear studies of DNA-bound water molecules and tritium NMR was expected to facilitate these investigations by eliminating the need to suppress the water resonance in tritium-detected 3H-1H NOESY experiments. We observed the anticipated through-space interactions found in B-form DNA in the NOESY experiments and an unexpected 'antiphase' cross-peak at the water frequency.