A chemical synthesis of a core fucose containing N-glycan was achieved. Asparagine was introduced at an early stage of the synthesis, and the sugar chain was convergently elongated. As for the ...fragment synthesis, we reinvestigated α-sialylation, β-mannosylation, and N-glycosylation to reveal that precise temperature control was essential for these glycosylations. Intermolecular hydrogen bonds involving acetamide groups were found to reduce the reactivity in glycosylations: the protection of NHAc as NAc2 dramatically improved the reactivity. The dodecasaccharide–asparagine framework was constructed via the (4 + 4) glycosylation and the (4 + 8) glycosylation using the tetrasaccharide donor and the tetrasaccharide–asparagine acceptor. An ether-type solvent enhanced the yields of these key glycosylations between large substrates. After the whole deprotection of the dodecasaccharide, the target N-glycan was obtained.
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. This review is mainly focused on the one-pot, double-click methodology (containing alkyne-azide click cycloaddition with the following 6π-azaelectrocyclization reactions) used in the synthesis of
-glycoconjugates. Homogeneous (including one type of biantennary
-glycan fragments) and heterogeneous (containing two to four types of biantennary
-glycan fragments) glycoclusters on albumin were synthesized via this strategy. A series of cell-, tissue- and animal-based experiments proved glycoclusters to be a very promising class of targeted delivery systems. Depending on the oligosaccharide units combined in the cluster, their amount, and arrangement relative to one another, conjugates can recognize various cells, including cancer cells, with high selectivity. These results open new perspectives for affected tissue visualization and treatment.
Recently, PET has been paid a great deal of attention as a non-invasive imaging method. In this review, the recent advances of PET using biomolecules, such as peptides, monoclonal antibodies, ...proteins, oligonucleotides, and glycoproteins will be described. So far, PET of biomolecules has been mainly used for diagnosis of cancers. The biomolecules have been conjugated with the DOTA ligand, labeled with radiometals as the beta+ emitter, and targeted to specific tumors, where they have enabled visualization of even small metastatic lesions, due to the high sensitivity of the PET scanners. Some of the biomolecules have been used not only for PET diagnosis, but also for radiotherapeutic treatments by simply changing the radiometals to beta(-) emitters. Collaborative work between chemists, biologists, and physicians will be important for the future of biomolecule-based targeting and diagnosis.
Alkyl esters, such as propargyl esters, typically lack the electron‐withdrawing inductive effects needed to participate in nucleophilic acyl substitution reactions. Herein, we report an unusual ...observation in which glycine propargyl ester derivatives displayed selective, base‐independent reactivity towards linear alkylamines under mild, metal‐free conditions. Through global reaction route mapping (GRRM) modeling calculations, it is predicted that these observations may be governed by factors related to hydrogen‐bonding and intermolecular interactions, rather than electron‐withdrawing inductive effects. Based on this concept of propargyl‐assisted selective amidation, a direct application was made to develop a novel site‐specific C‐terminal glycine peptide bioconjugation technique as a proof‐of‐concept, which relies upon the selective reactivity of glycine propargyl esters over that of aspartate and glutamate side‐chain‐linked propargyl esters.
Glycine propargyl esters show selective amidation activity with linear alkylamines, even in the absence of a base catalyst. Calculations suggest hydrogen‐bonding and intermolecular interactions play a central role for reactivity. Using these findings, applications to a site‐specific C‐terminal peptide conjugation technique is presented (see scheme).
Convenient and general method for live cell surface labeling was established. Azide-containing fluorescences were initially conjugated with the unsaturated ester aldehyde containing the ...dibenzocyclooctyne (DIBO), by the strain-promoted click reaction. The resulting probes were then treated with the live cells in one-pot process, efficiently labeling the surface lysines by azaelectrocyclization under the mild conditions.
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Clean surgical margins in breast‐conserving surgery (BCS) are essential for preventing recurrence. Intraoperative pathologic diagnostic methods, such as frozen section analysis and imprint cytology, ...have been recognized as crucial tools in BCS. However, the complexity and time‐consuming nature of these pathologic procedures still inhibit their broader applicability worldwide. To address this situation, two issues should be considered: 1) the development of nonpathologic intraoperative diagnosis methods that have better sensitivity, specificity, speed, and cost; and 2) the promotion of new imaging algorithms to standardize data for analyzing positive margins, as represented by artificial intelligence (AI), without the need for judgment by well‐trained pathologists. Researchers have attempted to develop new methods or techniques; several have recently emerged for real‐time intraoperative management of breast margins in live tissues. These methods include conventional imaging, spectroscopy, tomography, magnetic resonance imaging, microscopy, fluorescent probes, and multimodal imaging techniques. This work summarizes the traditional pathologic and newly developed techniques and discusses the advantages and disadvantages of each method. Taking into consideration the recent advances in analyzing pathologic data from breast cancer tissue with AI, the combined use of new technologies with AI algorithms is proposed, and future directions for real‐time intraoperative margin assessment in BCS are discussed.
Clean surgical margins in breast‐conserving surgery (BCS) are essential for preventing recurrence and repeat surgery. This work describes the advantages and disadvantages of conventional pathologic and newly developed techniques. Future directions and prospectives in real‐time intraoperative margin assessment in BCS as well as recent advances in deep learning and artificial intelligence algorithms are discussed.
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Acrolein, a highly reactive α,β-unsaturated aldehyde, is a compound to which humans are exposed in many different situations and often causes various human diseases. This paper ...summarizes the reports over the past twenty-five years regarding disease-associated acrolein detected in clinical patients and the role acrolein plays in various diseases. In several diseases, it was found that the increased acrolein acts as a pathogenetic factor. Thus, we propose the utility of over-produced acrolein as a substrate for a promising therapeutic or diagnostic method applicable to a wide range of diseases based on an in vivo synthetic chemistry strategy.
Ethiopia is at the edge of the distribution for African wild rice,
Oryza longistaminata
. Here, chloroplast (cp) and simple sequence repeat (SSR) markers were applied to wild rice accessions in ...Ethiopia to evaluate how they differ from control
O. longistaminata
,
O. barthii
and O.
glaberrima
accessions which originated from African countries. Based on the cp genomes of African wild rice species, maternally inherited cpINDEL markers were developed. The cp indels helped to elucidate 20 plastid types. African cultivated rice shared a particular plastid type with one of annual
O. barthii
. Parts of northern wild rice in Ethiopia shared Type 6 with control
O. longistaminata
. The north group shared another type with parts of the south group. The 16 SSR markers amplified a total of 155 alleles in 215 rice accessions, with mean allelic richness of 9.688 per locus, observed heterozygosity of 0.241, expected heterozygosity of 0.724, polymorphic information content of 0.700, and a significant genetic differentiation of 0.215. Both cpINDEL and nuclear markers analyses suggested that wild rice in Ethiopia belongs to
O. longistaminata
. However, they carry both a unique plastid type and different population structure from control
O. longistaminata
collected from other areas in Africa. We concluded that the edge of its distribution maintains unique variation. These populations are regarded as valuable genetic resources for future rice breeding.
•We investigated the influential factors governing stemflow by plantation teak trees.•Stemflow funneling ratio (SFFR) was analyzed by boosted regression tree analyses.•Event vapor pressure deficit ...was the top factor affecting stemflow for larger trees.•Rain duration was the leading factor affecting stemflow for smaller-sized teak trees.•The response of SFFR to increasing leaf area index was complex, differing among trees.
Stemflow (SF) has been recognized as an important process delivering water to spatially localized areas of the forest floor. Based on almost six years of daily SF data from nine teak trees in a Thai plantation, together with detailed above-canopy meteorological data and daily leaf area index (LAI) data, this study sought to better understand how specific biotic and abiotic factors affect both individual and stand-scale SF production from teak trees. Specifically, the factors affecting stemflow funneling ratio (SFFR) at individual and stand scales were analyzed and compared by means of boosted regression tree (BRT) analysis. The largest variation of SFFR among individual teak trees was observed in the leafed state. For trees taller than average, the BRT analysis revealed that vapor pressure deficit during rain was the most influential factor affecting SFFR. Vapor pressure deficit had a negative influence on SFFR, implying significant control of evaporative demand during rain. In contrast, for trees shorter than the average, rain duration (RD) was the most influential variable, having a positive correlation with SFFR. The stand-scale BRT analysis for all nine teak trees demonstrated that RD was the most influential factor affecting SFFR (exerting positive influence) but that an array of other factors (both abiotic and biotic) played intricate and complex roles in governing SFFR. The effect of LAI on SFFR was complicated and varied greatly among individual teak trees. It is possible that spatially heterogeneous flowpaths of intercepted water inside the teak canopy, which could be a product of the large-sized mature leaves of teak, may account for the tree-to-tree variation in the responses of SFFR to changing LAI. Although our study focused on teak trees, the demonstrated physically-based mechanistic explanations of stemflow production could apply to other even-aged deciduous forests and monospecific plantations.
For the stereoselective assembly of bioactive glycans with various functions, 1,2-
cis
-
O
-glycosylation is one of the most essential issues in synthetic carbohydrate chemistry. The
cis
-configured
...O
-glycosidic linkages to the substituents at two positions of the non-reducing side residue of the glycosides such as α-glucopyranoside, α-galactopyranoside, β-mannopyranoside, β-arabinofuranoside, and other rather rare glycosides are found in natural glycans, including glycoconjugate (glycoproteins, glycolipids, proteoglycans, and microbial polysaccharides) and glycoside natural products. The way to 1,2-
trans
isomers is well sophisticated by using the effect of neighboring group participation from the most effective and kinetically favored C-2 substituent such as an acyl group, although high stereoselective synthesis of 1,2-
cis
glycosides without formation of 1,2-
trans
isomers is far less straightforward. Although the key factors that control the stereoselectivity of glycosylation are largely understood since chemical glycosylation was considered to be one of the useful methods to obtain glycosidic linkages as the alternative way of isolation from natural sources, strictly controlled formation of these 1,2-
cis
glycosides is generally difficult. This minireview introduces some of the recent advances in the development of 1,2-
cis
selective glycosylations, including the quite recent developments in glycosyl donor modification, reaction conditions, and methods for activation of intermolecular glycosylation, including the bimodal glycosylation strategy for 1,2-
cis
and 1,2-
trans
glycosides, as well as intramolecular glycosylations, including recent applications of NAP-ether-mediated intramolecular aglycon delivery.
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