Stimulus-responsive
molecules that modify nucleic acids in a site- and base-selective manner play
an important role for genomic research. N-Acetyl-7-nitroindoline is a characteristic in
that its acetyl group is photo-activated to acetylate amines to form amides. In
this study, the N-acetyl-7-nitroindoline
part was connected to the 2´-deoxyribose part, which was incorporated into the oligodeoxynucleotide
probes, and their photo-reactivities toward the complementary RNA were
investigated. One probe was photo-activated to deacetylate to the nitroso
derivative. Photo-activation of another probe induced acetylation of the RNA. An
interesting finding was the cross-link formation of another probe with the RNA strand.
Nitrogen dioxide has been used
as an oxidant and nitrating reagent in organic synthesis. However, its use is
limited because it is harmful and hard to handle. Iron(III) nitrate nonahydrate
has attracted attention as a source of nitrogen dioxide because it is a readily
available reagent of low toxicity and cost. This paper describes development of
nitrolactonization mediated by iron nitrate as a source of nitrogen dioxide. Nitrolactones
obtained by this reaction could lead to useful compounds, such as
1,2-aminoalcohol and amino acid derivatives bearing a tetrasubstituted carbon
center.
Peptide/protein thioesters function as an
indispensable synthetic intermediate in Native Chemical Ligation (NCL) that has
enjoyed great success in the chemical synthesis of proteins. Facile conversion
of recombinant proteins to thioesters allows for the straightforward access to
semi-synthetic proteins with chemically synthesized peptides used as an NCL
partner. In this paper, the authors developed an efficient thioester-producing
protocol. The protocol features the traceless conversion of the CysPro triple
repeat–Leu-OH-tagged sequence to the corresponding thioesters by treatment with
carboxypeptidase Y in the presence of hydrazine followed by an auto-processing
of the CysPro units.
Molecular imprinting has been broadly perceived as the most advanced
technology for preparing various materials that have a specific recognition
site with selective adsorption. MIPs (Molecular Imprinted Polymer) are
three-dimensional polymers with specific recognition sites for a certain
molecule. A MIP is formed by crosslinking template with monomers to create
copolymers. For every MIP, each template:monomer:crosslinker ratio shows a distinct
performance for a specific analyte. Ratio effect on analytical performances are
briefly outlined in this review. From all reports in this review, the synthesis
of MIP using a template:monomer:crosslinker ratio of 1:4:20 is more likely to
provide optimal imprinting efficiency.
With
the globalization of the drug supply chain, the quality assurance of drugs is
required worldwide. Pharmacopoeias provide public standards for the drug quality
assurance, and smooth incorporation of the concepts of the international
guidelines into pharmacopoeias is desired. In particular, impurities in drugs
are to be controlled to ensure patient safety. The authors focused on the
harmonized guidelines for residual solvents, elemental impurities, and
mutagenic impurities, and proposed an approach for promoting incorporation of
the concepts of the guidelines into pharmacopoeias by combining the cause and
effect analysis and the logic model.
In
clinical practice, a thickening solution is frequently used to allow easy
swallowing of tablets as well as foods by patients suffering from dysphagia. This
study
investigated the effect of thickening solution on tablet disintegration. Model tablets
containing different disintegrants were prepared and their disintegration times
were measured. The tablet disintegration times were
significantly prolonged by immersion in thickening
solution containing xanthan gum and the degree of prolongation differed depending on
the type of disintegrant
contained in the tablets. These findings provide valuable information for
design of tablet formulation and clinical medication
management for older patients with dysphagia.
Chlorofluoroacetamide (CFA) shows
chemically tuned mild reactivity that is suitable as an electrophilic warhead
for highly target selective covalent inhibitors. Assembly of a small set of
CFA-appended fragment library and its screening against cysteine protease
papain demonstrated the potential utility of CFA in novel covalent drug
discovery using a fragment-based approach.
This
review describes development of innovative reactions utilizing the
characteristic reactivity of oxygen atoms, 1) asymmetric synthesis of chiral quaternary
carbon centers, 2) asymmetric synthesis using acetal functions, and 3) organic
chemistry using acetal-type reactive salt chemical species, and their
application to the asymmetric synthesis of natural products such as
Fredericamycin A, anthracycline antibiotics, scyphostatin, Sch 642305, stenin, claboronin,
rubrenolide, rubrynolide, centrolobine, and decytospolides A and B, etc. In
particular, reactions using acetal-type reactive salt chemical species can
alter the retrosynthesis planned based on conventional reactions because they allow
the coexistence of functional groups that normally cannot coexist.
Binding
assays are widely used to study the estrogenic activity of endocrine-disrupting
chemicals targeting the estrogen receptor (ER). In this study, the authors synthesized benzofurazan-labeled estradiol
(BD-E2) derivatives as a fluorescent ligand for ER binding assays. BD-E2
compounds exhibit spectroscopic properties with high fluorescence intensities
and large Stokes shifts in a hydrophobic environment. Analysis of the fluorescent
ligands and human recombinant ER interactions revealed that the fluorescence
intensity increased in hydrophobic environments, such as the receptor-binding
site. By evaluation of the bound ligands based on changes in the fluorescence
intensity, the authors established a simple,
rapid, reliable ER binding assay.
An extemporaneous preparation, sodium
dantrolene granules, has been manufactured using planetary centrifugal
granulation method in the pharmacy. The amount of water was determined based on
plastic limit value of the formulation, which is a critical parameter of the
granulation method. The granulation process completes within 45 s, followed by
coating process (20 s). The resultant granules show sharp particle size
distribution and excellent flowability. The bulky powder was reformulated to the
granules with non-adhesive and free-flowing properties. Thus, the granulation
improves the usability of the medicine in the dispensing and dosing processes.
The quaternary nitrogen (N-Q) has been found to be
an effective adsorption site for nitrate ions. However, in addition to N-Q, there
are many functional groups such as C-π sites on activated carbon fibers (ACFs),
and these functional groups have various effects on the adsorption capacity. Understanding
the properties of functional groups other than N-Q can be expected to further
improve ACFs adsorption performance. In this paper, the authors prepared the ACFs
with and without N-Q and examined their adsorption properties.
The fungal meroterpenoid
biosynthetic pathways exhibit an abundance of unusual chemistries and
interesting enzyme reactions, including those of the multi-functional non-heme Fe(II)- and 2-oxoglutarate-dependent oxygenases that
perform selective C–H activation/functionalization
with unusual substrate promiscuity and catalytic versatility. Structure–function studies of these remarkable enzymes provide
an excellent platform for the development of useful biocatalysts for synthetic
biology to create novel molecules for drug discovery.
Rubbing actions are often conducted to apply
topical formulations onto the skin. However,
few studies have reported the reasons for the acceleration of drug permeation
through skin after topical application with or without rubbing. In addition, no
studies observed the effect of rubbing direction on the skin
penetration-enhancement effects. In this paper, the
authors investigated the
effects of rubbing direction on the skin permeation and disposition of a model
hydrophilic drug, caffeine. This paper provides useful
information on the effect of rubbing action and rubbing
direction on the skin permeation of topically applied drugs.
Marine dinoflagellates are well known as rich
sources of biologically active compounds possessing unique chemical structures.
This paper deals isolation and structure elucidation of two new cytotoxic 15-membered
macrolides, iriomoteolodes-14a and 14b, from the marine dinoflagellate Amphidinium
species collected off Iriomote Island, Okinawa. The structures including the
absolute stereochemistry of eight stereocenters were determined on basis of
spectroscopic data and chemical conversion method. These compounds are
analogous to known macrolides, amphidinolides O and P, and the biosynthetic
relationships for four compounds are also described.
Quantitative nuclear magnetic resonance is
a powerful tool in quantitative determination of the main component and
impurities in a drug substance or a drug product because of its high accuracy,
precision and efficiency. This method has the potential to establish
metrological traceability easily and expected to be widely utilized for some compendial guidelines and official
standards. In this study, the authors conducted
an inter-laboratory comparison for qNMR methodology and confirmed that statistically
qNMR has the competence to obtain the same quantification performance and
accuracy as the conventional reliable methods.
Tyrosyl radical
generation plays a major role in hemin/peroxide-induced oxidative stress. The authors developed a
method for trapping tyrosyl radicals using a derivative of N-methyl
luminol, a tyrosine labeling reagent. The
derivative selectively forms a covalent bond with tyrosine residue (tyrosine
click reaction) under single-electron oxidation conditions. This reaction
labels oxidative stress hotspots not only at the protein level but also at the
level of tyrosine residues undergoing oxidation. The cover picture depicts
an image of tyrosine click reaction to aid in the visualization of
hemin/peroxide-induced oxidative stress generated in blood vessels.
Amine
groups occur widely in many naturally abundant chemicals and artificial functional
molecules. Efficient C–N bond conversion methods suitable for late-stage
functionalization would greatly expand their synthetic utility. However,
transformation of C–N bond is generally difficult, due to the high stability. Ammonium salt is an ideal pre-activation form for
amine, since it can be obtained quantitatively from amine via simple protocol.
In this review, synthetic transformations through ammonium C–N bond cleavage developed by the author’s group are
summarised, describing a new trend for utilization of amine in organic
synthesis.
The authors previously reported
novel β-galactosidase activity in the human Golgi apparatus and predicted the precursor
GLB1 isoform 1 as the enzyme responsible for this activity. GLB1
isoform 1 is involved in lysosomal storage diseases and widely used as a
biomarker of cellular senescence. Inhibitor-derived chemical probes may serve as powerful
tools for identifying the enzyme. In this study, the authors screened
inhibitors from two compound libraries. One of the
obtained inhibitors showed increased inhibitory activity following redesigning
using molecular docking simulations. This inhibitor may
be useful for developing chemical probes to identify the enzyme discovered
by the authors.
Honey produced from manuka in New Zealand
has exceptionally high antibacterial activity and is approved as a medicine for
wound care. In this paper, authors developed a simple and rapid evaluation
method for the antibacterial activity of manuka honey by using a fluorescence
fingerprint (excitation and emission matrix). Three distinct wavelength
combinations of fluorescence were obtained from the honey samples. A
correlation between the fingerprint and the antibacterial activity was
indicated by a multivariate analysis, and authors succeeded in the evaluation
of the activity from the fingerprint. Furthermore, some chemicals (leptosperin
and leptosperin) were indicated as antibacterial compounds in the honey.
There are a lot of medicines having anticholinergic actions as side
effect. However, it is sometimes difficult to examine side effect only in
clinical studies because of various limitations. Therefore, the authors tried
to predict anticholinergic activity on the basis of compound’s structures by quantitative structure-activity relationship (QSAR) and docking study. These methods might be
helpful for risk assessment of anticholinergic side effects.