4-(2,5-Dimethyl-1H-pyrrol-1-yl)-N-(2,5-dioxopyrrolidin-1-yl) benzamide improves monoclonal antibody production in a Chinese hamster ovary cell culture

There is a continuous demand to improve monoclonal antibody production for medication supply and medical cost reduction. For over 20 years, recombinant Chinese hamster ovary cells have been used as a host in monoclonal antibody production due to robustness, high productivity and ability to produce proteins with ideal glycans. Chemical compounds, such as dimethyl sulfoxide, lithium chloride, and butyric acid, have been shown to improve monoclonal antibody production in mammalian cell cultures. In this study, we aimed to discover new chemical compounds that can improve cell-specific antibody production in recombinant Chinese hamster ovary cells. Out of the 23,227 chemicals screened in this study, 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N-(2,5-dioxopyrrolidin-1-yl) benzamide was found to increase monoclonal antibody production. The compound suppressed cell growth and increased both cell-specific glucose uptake rate and the amount of intracellular adenosine triphosphate during monoclonal antibody production. In addition, the compound also suppressed the galactosylation on a monoclonal antibody, which is a critical quality attribute of therapeutic monoclonal antibodies. Therefore, the compound might also be used to control the level of the galactosylation for the N-linked glycans. Further, the structure-activity relationship study revealed that 2,5-dimethylpyrrole was the most effective partial structure of 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N-(2,5-dioxopyrrolidin-1-yl) benzamide on monoclonal antibody production. Further structural optimization of 2,5-dimethylpyrrole derivatives could lead to improved production and quality control of monoclonal antibodies

Hysteretic Tricolor Electrochromic Systems Based on the Dynamic Redox Properties of Unsymmetrically Substituted Dihydrophenanthrenes and Biphenyl-2,2 '-Diyl Dications: Efficient Precursor Synthesis by a Flow Microreactor Method

A series of biphenyl-2, 2'-diylbis(diarylmethanol)s 3, which have two kinds of aryl groups at the bay region, were efficiently obtained by integrated flow microreactor synthesis. The diols 3NO/NX are the precursors of unsymmetric biphenylic dications 2NO/NX^[2+] which are transformed into the corresponding dihydrophenanthrenes 1NO/NX via 2NO/NX^[+•] upon reduction, when they exhibit two-stage color changes. On the other hand, the steady-state concentration of the intermediate 2NO/NX^[+•] is negligible during the oxidation of 1NO/NX to 2NO/NX^[2+], which reflects unique tricolor electrochromicity with a hysteretic pattern of color change [color 1→color 2→color 3→color 1]

Complexation-induced inversion of helicity by an organic guest in a dynamic molecular propeller based on a tristerephthalamide host with a two-layer structure

A tristerephthalamide host exhibited two helical geometries with (M)- and (P)- helicity, respectively, in terms of the twisting direction of a two-layer structure, and the helical preference switched upon complexation with a ditopic guest. In both uncomplexed and complexed states, the intramolecular transmission of chirality was responsible for the control of helicity

Enhanced circular dichroism at elevated temperatures through complexation-induced transformation of a three-layer cyclophane with dualistic dynamic helicity

When two planes stacked one above the other are twisted, they provide a dynamic pair of helical conformations with (M)- or (P)-helicity. We designed a three-layer cyclophane that consists of two such dynamic pairs: the top and middle planes, and the middle and bottom planes. Hence, several global conformations could be created for the overall molecule, e.g., double-helical forms with a pair with the same helicity [(M, M) or (P, P)], and a meso-like form with a pair with a different helicity (M, P). These conformations dynamically interconvert to each other in solution. Chiroptical properties were given by the helical-sense preference of the double-helical forms, which was brought about through complexation with a chiral hydrogen-bonding guest. In terms of the conformational energy in a complexed state, when a desirable relationship between double-helical and meso-like forms was attained, complexation-induced circular dichroism was enhanced at elevated temperatures and decreased at lowered temperatures

Controllability of dynamic double helices: quantitative analysis of the inversion of a screw-sense preference upon complexation

We describe a quantitative analysis of the complexation-induced inversion of a screw-sense preference based on a conformationally dynamic double-helix structure in a macrocycle. The macrocycle is composed of two twisting units (terephthalamide), which are spaced by two strands (1,3-bis(phenylethynyl)benzene), and is designed to generate a double-helix structure through twisting about a C-2 axis in a conrotatory manner. The attachment of chiral auxiliaries to the twisting units induces a helical preference for a particular sense of (M)- or (P)-helicity through the intramolecular transmission of chirality to dynamic double helices. The twisting unit can also act as a binding site for capturing a guest molecule, and, in a complexed state, the preferred screw sense of the dynamic double-helix structure is reversed to exhibit the contrary preference. We quantitatively monitored the complexation-induced inversion of the screw-sense preference using H-1 NMR spectroscopy, which enabled us to observe independently two species with (M)- or (P)-helicity in both the absence and presence of a guest molecule. Inversion of the screw-sense preference was induced upon complexation with an achiral guest as well as a chiral guest

Supramolecular chiroptical switching of helical-sense preferences through the two-way intramolecular transmission of a single chiral source associated with a dynamic helical loop

We demonstrate a chiroptical switching system with a simple molecule. The molecule contains a pair of chromophores of diphenylacetylene that are linked with a diyne bond and arranged to exert exciton coupling in helically folded forms with (M)- or (P)-helicity. A tertiary amide group is attached to each end of the looped molecule. The amide carbonyls were used to capture a ditopic hydrogen-bonding guest. A chiral auxiliary group on the amide nitrogen acted as a chiral handle to control the helical-sense preference of dynamic helical forms of the loop. The helical-sense preference is brought about by an intramolecular transmission of point chirality associated with the loop. The preferred sense was switched upon complexation with an achiral additive through the formation of hydrogen bonds. In both states, before and after complexation, the helical-sense preferences were controlled through two-way transmission of the single chiral source.アクセプト後にタイトル変更あり、著者最終稿は変更前のタイトル"Supramolecular chiroptical switching of helical-sense preferences through the two-way intramolecular transmission of a single chiral source associated with a dynamic helical loop

Designed molecular propellers based on tetraarylterephthalamide and their chiroptical properties induced by biased helicity through transmission of point chirality

The syn-atropisomers of the title bis(tertiary amide)s were designed as six-bladed molecular propellers based on the directing effects of amide dipoles; the helicity of the propeller is biased to prefer one handedness upon the attachment of point chirality to the amide nitrogens to attain stronger circular-dichroism activity than for the non-propeller-shaped anti-isomers

A stereoselective method for the construction of the C8′–O–C6″ ether of nigricanoside-A: synthesis of simple models for the C20 lipid chain/galactosyl glycerol segment

A method for the stereoselective construction of the C8′–O–C6″ ether of nigricanoside-A, an antimitotic natural product from the green alga Avrainvillea nigricans, has been developed based on chirality-transferring Ireland–Claisen rearrangement. The method was successfully applied to the synthesis of simple models for the C20 lipid chain/galactosyl glycerol segment of the natural product