TCIメール No.181 | 東京化成工業株式会社

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1 TCI メール 2019 年夏号 l o. 181 目次製品紹介 12 寄稿論文 2 Poly(2-oxazoline)s: The Versatile Polymer Platform Victor R. de la Rosa and Richard Hoogenboom 化学よもやま話研究室訪問記 10 科学クラブを訪ねて ~ 第 36 回化学クラブ研究発表会 ~ 有機合成に使用できる金属ナトリウム分散体骨芽細胞の分化を促進する低分子化合物 (TH) 自然界に少量しか存在しない四炭糖 SIRT2 阻害剤 SIRT1 および 2 阻害剤 CASA 試薬 : 新しいキラル MR シフト試薬 ISS CDE:TCIMCV

2 TCI メール 2019 年夏号 l o. 181 寄稿論文 Poly(2-oxazoline)s: The Versatile Polymer Platform Victor R. de la Rosa and Richard Hoogenboom Abstract: Poly(2-oxazoline)s (commonly abbreviated as PAx, PZ, Px or PXA) represent an extraordinary polymer platform with highly tunable properties and excellent biocompatibility, making them interesting in a broad variety of applications. The ability to vary the solubility and properties of PAx via the side-chains is a highly interesting feature to be exploited for determining structure property relationships. The polymer hydrophilicity can be tuned from superhydrophilic via thermoresponsive to hydrophobic. End-functional PAx can be used as macroinitiators for block copolymer synthesis, or to confer the polymer properties (anti-fouling, thermoresponsive, etc.) to a substrate of interest. The high stability of PAx against degradation is an important advantage of this polymer class with respect to surface functionalization applications. Besides surface and nanoparticle functionalization, clickable and amino end-functional PAx allow further modification and conjugation to a wide range of moieties, e.g., probes or biomolecules, using a variety of highly efficient coupling chemistries. The present article intends to provide an overview of the aforementioned application possibilities of PAx focusing on examples involving readily available PAx derivatives. Keywords: poly(2-oxazoline)s, polymer platform, biocompatibility, terminal modification, conjugation 1. Introduction Poly(2-oxazoline)s (commonly abbreviated as PAx, PZ, Px or PXA) represent an extraordinary polymer platform with highly tunable properties, making them interesting as basis for future materials. First reported years ago, PAx reemerged in the new millennium due to improved synthetic methodologies and excellent biocompatibility, allowing their use in a broad variety of applications. 1 The structural analogy of PAx with natural polypeptides accounts for their excellent biocompatibility and stealth-behavior i.e. PAx can be used to suppress interactions with proteins and cells which, in fact, is the key property that was at the basis of the wide-spread use of poly(ethylene glycol) (PEG). The properties of PAx can be adjusted by simply varying the polymer side-chains. Glass transition temperature (T g ) can be varied from -10 to 80 C using simple monomers 2 while solubility can be tuned from highly water soluble (poly(2-methyl- 2-oxazoline) (PMex) and poly(2-ethyl-2-oxazoline) (PEtx)) to thermoresponsive in water (poly(2-propyl-2- oxazoline) (PPrx) derivatives) or water insoluble (PAx with butyl of longer side chains) (Figure 1). 2

3 o. 181 l 2019 年夏号 TCI メール Figure 1. A series of PAx derivatives displaying their structural analogy with polypeptides and their amphiphilic character. PAx cover a broad lower critical solution temperature (LCST) range that can be finely tuned by copolymerization. PiPrx and PnPrx are structural isomers and potential alternatives to PIPAM (LCST = 32 C) (Adapted with permission from ref. 3). PAx can be prepared via living cationic ring-opening polymerization resulting in well-defined polymers with controlled end-groups that can be installed through initiation and termination (Figure 2). Under appropriate polymerization conditions, each initiator molecule initiates one polymer chain and all chains grow with a similar rate while chain transfer and chain termination do not occur, or are strongly suppressed. As a result, all polymer chains will have similar chain length and the ratio of monomer to initiator will determine the degree of polymerization (DP) at a certain monomer conversion. R S R 1 initiation Ts - n-1 R 1 Ts - + R n-1 R + propagation R 1 R 1 R 1 E termination R R 1 n E TsR Figure 2. verview of the cationic ring-opening polymerization (CRP) of 2-substituted-2-oxazolines, displaying the facile introduction of functionality at both the polymer chain-ends and side-chains. 2. Structure-property screening and formulation The ability to vary the solubility and properties of PAx via the side-chains is a highly interesting feature to be exploited for determining structure property relationships. Especially, the comparison of PMex, PEtx and P n Prx allows screening over a wide range of aqueous solubility, from PMex that is more hydrophilic than PEG, via PEtx that has similar aqueous solubility as PEG to P n Prx that is only soluble in water below 25 C, above which it undergoes an LCST transition. PMex-H, PEtx-H and P n Prx-H with a DP of 100 and a hydroxyl group at the omega-terminus are available in the TCI catalog (Figure 3), and provide an excellent platform for deriving fundamental structure property relationships, either for direct formulation or for further modification and coupling reactions. 3

4 TCI メール 2019 年夏号 l o. 181 Figure 3. Hydroxy-terminated poly(2-oxazoline)s available in the TCI catalog. The hydrogen bonding layer-by-layer assembly of PAx with tannic acid was reported to be strongly dependent on the hydrophilicity of the PAx, as PMex revealed purely enthalpic, hydrogen bonding driven assembly while P n Prx showed a purely entropy driven assembly based on the release of hydrating water molecules. PEtx exhibited an intermediate behavior. 4 Furthermore, Khutoryanskiy et al. functionalized Si 2 nanoparticles with PMex, PEtx and P n Prx and investigated their permeation and diffusion through mucosal tissue. 5 The authors found a clear correlation between polymer hydrophilicity and permeability through the mucosal barrier, whereby the most hydrophilic PMex-grafted Si 2 nanoparticles permeated significantly faster and deeper into the mucosa than their more hydrophobic PEtx and P n Prx-grafted counterparts. A final example consists of the grafting of PMex, PEtx or P n Prx on gold nanoparticles, revealing that their aggregation behavior can be strongly altered by changing the PAx side chains Poly(2-oxazoline) partial hydrolysis Defined PAx homopolymers can also be used for (partial) hydrolysis, 7 yielding poly(2-oxazoline)-copolyethylenimine copolymers or linear polyethylenimine (L-PEI). 8 Partially hydrolyzed PAx may serve as functional materials in which the secondary amine units in the main chains can be further modified to, e.g., install methyl ester functionalities as additional reactive handles (see Figure 4). 9 Full hydrolysis followed by full reacylation has also been demonstrated to yield novel PAx that are not easily attainable via CRP. 10 Furthermore, partially hydrolyzed P n Prx has been exploited as thermoresponsive gene delivery vector. 11 n H stat H H a) HClaq, Δ R n-m m b) ah aq Cl n-m stat R H m Figure 4. Partial hydrolysis of poly(2-ethyl-2-oxazoline) and subsequent functionalization. 4

5 o. 181 l 2019 年夏号 TCI メール 4. End-group modification Chain-end functionalized PAx offer an excellent platform for derivatization at the polymer termini allowing, e.g., facile grafting to (bio)molecules, surfaces and particles. In virtue of their high stability and biocompatibility, PAx functionalized surfaces 12 and nanoparticles 6 have potential uses in a variety of applications including implants, biosensors, imaging, or drug delivery. 3 In analogy to PEG, end-functional PAx have been successfully conjugated to biologicals for half-life extension, protection against degradation and immunogenicity prevention. 3,13 With over fifteen PEGylated pharmaceuticals in the market, PEG has proven extremely effective; however, its immunogenicity has become a significant issue, limiting further development of novel PEGylated therapeutics. 14 Thus, considering the biocompatibility and versatility of PAx, PAxylation or PZylation has been proposed as the new generation PEGylation. 14a,15 The previously mentioned PEtx and PMex-H have been used for conjugation to polylysine (PLL), after conversion of the hydroxyl group to a carboxyl group via ring-opening of succinic anhydride. Subsequent coating of the PAx-PLL induced efficient non-fouling properties to the substrate, whereby the PMex-g-PLL resulted in more efficient suppression of protein and cell adhesion compared to PEG PLL and PEtx-PLL (Figure 5). 16 Figure 5. Surface functionalization with brush-forming PLL graft copolymers with different side-chain compositions (Adapted with permission from ref. 16a). PEtx-H has also been demonstrated as efficient initiator for the controlled ring-opening of cyclic esters, directly yielding amphiphilic block copolymers. 17 Such block copolymers may be utilized for the encapsulation of drugs and their slow release based on hydrolysis of the polyester block. 5

6 TCI メール 2019 年夏号 l o. 181 H n m R TU, DBU CHCl 3 n R H m Figure 6. Schematic representation of the synthetic method for the preparation of block copolymers composed of 2-oxazolines and (functional) 6-membered cyclic carbonates. 17 Besides the hydroxyl end-groups, azides and amino end-groups can be installed in PAx through termination and post-polymerization functionalization, further expanding the conjugation possibilities. 18 Clickable PAx- 3 polymers enable efficient further modification via copper(i) catalyzed azide-alkyne cycloadditions with alkyne functionalized compounds, substrates or materials, as well as through strain-promoted azide-alkyne cycloadditions with strained alkynes. 19 PMex and PEtx with amine (-H 2 ) end-functionalities allow the conjugation of the polymer to a wide range of moieties and substrates. PAx-H 2 can be easily reacted through a variety of chemistries such as activated esters, or iso(thio)cyanates. For example, substrates decorated with epoxides have been rendered protein repellent or antifouling by reaction with PEtx-H The distinctly high chemical stability of PAx makes them especially interesting for surface functionalization. 21 Figure 7 showcases some of the chemistries that enable the formation of stable poly(2-oxazoline) conjugates based on these functional hydrophilic polymers, which are currently available in the TCI catalog. CLICKABLE PLY(2-XAZLIE)S 3 3 R 2 CuAAC or SPAAC R 1 R 2 or R 1 R 2 AMIE PLY(2-XAZLIE)S iso(thio)cyanates H 2 R 2 C S or activated esters R 2 R 1 H S H R 2 or R 1 H R 2 H 2 R 3 or epoxides R 2 H H R 2 etc. R 1 Figure 7. Conjugation reactions involving clickable and amine-functional poly(2-oxazoline)s. Amine-terminated poly(2- oxazoline)s can be used in combination with multiple other functional groups such as anhydrides, carbonates, aldehydes, etc. 6

7 o. 181 l 2019 年夏号 TCI メール 6. Conclusions The biocompatibility, tunable properties and high functionalization possibilities of PAx make them a very attractive polymer platform for a broad spectrum of applications, ranging from biomedicine to smart materials and from personal care, via cosmetics to pharmaceuticals. The availability of PMex-H, PEtx-H and P z Prx-H with DP100 at TCI allows fast and efficient screening of the effect of polymer solubility on their formulation behavior and effectiveness for various applications. Moreover, they may serve as starting materials for the controlled (partial) hydrolysis towards functional PAx. The chain-end-functionalized PAx that are available with hydroxyl, azide and amino end-groups allow further modification and conjugation to a wide range of moieties, e.g., biomolecules such as proteins and surfaces or (nano)particles. 文献 1. (a) H. Schlaad, R. Hoogenboom, Poly(2-oxazoline)s and Related Pseudo-Polypeptides. Macromol. Rapid Comm. 2012, 33, (b) R. Hoogenboom, years of poly(2-oxazoline)s. Eur. Polym. J. 2017, 88, (a) B. Verbraeken, B. D. Monnery, K. Lava, R. Hoogenboom, The chemistry of poly(2-oxazoline)s. Eur. Polym. J. 2017, 88, 451. (b) M. Glassner, M. Vergaelen, R. Hoogenboom, Poly(2-oxazoline)s: A comprehensive overview of polymer structures and their physical properties. Polym. Int. 2017, 67, V. R. de la Rosa, Poly(2-oxazoline)s as materials for biomedical applications. J. Mater. Sci: Mater. M. 2014, 25, A. Sundaramurthy, M. Vergaelen, S. Maji, R. Auzély-Velty, Z. Zhang, B. G. De Geest, R. Hoogenboom, Hydrogen Bonded Multilayer Films Based on Poly(2-oxazoline)s and Tannic Acid. Adv. Healthcare Mater. 2014, 3, E. D. H. Mansfield, V. R. de la Rosa, R. M. Kowalczyk, I. Grillo, R. Hoogenboom, K. Sillence, P. Hole, A. C. Williams, V. V. Khutoryanskiy, Side chain variations radically alter the diffusion of poly(2-alkyl-2- oxazoline) functionalised nanoparticles through a mucosal barrier. Biomater. Sci. 2016, 4, V. R. de la Rosa, Z. Zhang, B. G. De Geest, R. Hoogenboom, Colorimetric Logic Gates Based on Poly(2- alkyl-2-oxazoline)-coated Gold anoparticles. Adv. Funct. Mater. 2015, 25, V. R. de la Rosa, E. Bauwens, B. D. Monnery, B. G. De Geest, R. Hoogenboom, Fast and accurate partial hydrolysis of poly(2-ethyl-2-oxazoline) into tailored linear polyethylenimine copolymers. Polym. Chem. 2014, 5, M. A. Mees, R. Hoogenboom, Full and partial hydrolysis of poly(2-oxazoline)s and the subsequent postpolymerization modification of the resulting polyethylenimine (co)polymers. Polym. Chem. 2018, 9, M. A. Mees, R. Hoogenboom, Functional Poly(2-oxazoline)s by Direct Amidation of Methyl Ester Side Chains. Macromolecules 2015, 48, Sedlacek,. Janouskova, B. Verbraeken, R. Hoogenboom, Straightforward Route to Superhydrophilic Poly(2-oxazoline)s via Acylation of Well-Defined Polyethylenimine. Biomacromolecules 2019, 20, M. Mees, E. Haladjova, D. Momekova, G. Momekov, P. S. Shestakova, C. B. Tsvetanov, R. Hoogenboom, S. Rangelov, Partially Hydrolyzed Poly(n-propyl-2-oxazoline): Synthesis, Aqueous Solution Properties, and Preparation of Gene Delivery Systems. Biomacromolecules 2016, 17,

8 TCI メール 2019 年夏号 l o H. Bludau, A. E. Czapar, A. S. Pitek, S. Shukla, R. Jordan,. F. Steinmetz, Pxylation as an alternative stealth coating for biomedical applications. Eur. Polym. J. 2017, 88, (a) R. Luxenhofer, Y. Han, A. Schulz, J. Tong, Z. He, A. V. Kabanov, R. Jordan, Poly(2-oxazoline)s as Polymer Therapeutics. Macromol. Rapid Commun. 2012, 33, (b) T. X. Viegas, M. D. Bentley, J. M. Harris, Z. Fang, K. Yoon, B. Dizman, R. Weimer, A. Mero, G. Pasut, F. M. Veronese, Polyoxazoline: Chemistry, Properties, and Applications in Drug Delivery. Bioconjugate Chem. 2011, 22, (a) K. Knop, R. Hoogenboom, Fischer, U. S. D. Schubert, Poly(ethylene glycol) in Drug Delivery: Pros and Cons as Well as Potential Alternatives. Angew. Chem. Int. Ed. 2010, 49, (b) Q. Yang, S. K. Lai, Anti- PEG immunity: emergence, characteristics, and unaddressed questions. WIREs anomed. anobiotechnol. 2015, 7, A. Magarkar, T. Róg, A. Bunker, A computational study suggests that replacing PEG with PMZ may increase exposure of hydrophobic targeting moiety. Eur. J. Pharm. Sci. 2017, 103, (a) G. Morgese, B. Verbraeken, S.. Ramakrishna, Y. Gombert, E. Cavalli, J.-G. Rosenboom, M. Zenobi- Wong,. D. Spencer, R. Hoogenboom, E. M. Benetti, Chemical Design of on-ionic Polymer Brushes as Biointerfaces: Poly(2-oxazine)s utperform Both Poly(2-oxazoline)s and PEG. Angew. Chem. Int. Ed. 2018, 57, (b) G. Morgese, E. Cavalli, J.-G. Rosenboom, M. Zenobi-Wong, E. M. Benetti, Cyclic Polymer Grafts That Lubricate and Protect Damaged Cartilage. Angew. Chem. Int. Ed. 2018, 57, V. R. de la Rosa, S. Tempelaar, P. Dubois, R. Hoogenboom, L. Mespouille, Poly(2-ethyl-2-oxazoline)- block-polycarbonate block copolymers: from improved end-group control in poly(2-oxazoline)s to chain extension with aliphatic polycarbonate through a fully metal-free ring-opening polymerisation process. Polym. Chem. 2016, 7, (a) S. sawa, T. Ishii, H. Takemoto, K. sada, K. Kataoka, A facile amino-functionalization of poly(2- oxazoline)s distal end through sequential azido end-capping and Staudinger reactions. Eur. Polym. J. 2017, 88, 553. (b) G. Volet, T. Lav, J. Babinot, C. Amiel, Click-Chemistry: An Alternative Way to Functionalize Poly(2-methyl-2-oxazoline). Macromol. Chem. Phys. 2011, 212, H. Bludau, A. E. Czapar, A. S. Pitek, S. Shukla, R. Jordan,. F. Steinmetz, Pxylation as an alternative stealth coating for biomedical applications. Eur. Polym. J. 2017, 88, L. Tauhardt, M. Frant, D. Pretzel, M. Hartlieb, C. Bücher, G. Hildebrand, B. Schröter, C. Weber, K. Kempe, M. Gottschaldt, Amine end-functionalized poly(2-ethyl-2-oxazoline) as promising coating material for antifouling applications. J. Mater. Chem. B 2014, 2, R. Konradi, C. Acikgoz, M. Textor, Polyoxazolines for onfouling Surface Coatings A Direct Comparison to the Gold Standard PEG. Macromol. Rapid Comm. 2012, 33, 関連製品 ULTRXA Poly(2-methyl-2-oxazoline) (n=approx. 100) 200mg 8,0 P26 ULTRXA Poly(2-methyl-2-oxazoline) Amine Terminated (n=approx. ) 100mg 10,900 0mg 38,200 U0135 ULTRXA Poly(2-methyl-2-oxazoline) Azide Terminated (n=approx. ) 100mg 10,900 0mg 38,200 U0134 ULTRXA Poly(2-ethyl-2-oxazoline) (n=approx. 100) 0mg 22,0 P27 ULTRXA Poly(2-ethyl-2-oxazoline) Amine Terminated (n=approx. ) 100mg 9,400 0mg 32,800 U0133 ULTRXA Poly(2-ethyl-2-oxazoline) Azide Terminated (n=approx. ) 100mg 9,400 0mg 32,800 U0132 ULTRXA Poly(2-propyl-2-oxazoline) (n=approx. 100) 200mg 9,000 P28 8

9 o. 181 l 2019 年夏号 TCI メール 執筆者紹介 Victor R. de la Rosa Victor R. de la Rosa studied Chemistry at the University of Valladolid (UVa; Spain) and Ghent University (UGent; Belgium), where he spent a year within the Erasmus programme. Upon graduating in 2010, he returned to Ghent to conduct a PhD on poly(2-oxazoline)s and supramolecular chemistry under the supervision of Prof. Richard Hoogenboom. In 2015, he was awarded an IWT post-doctoral grant (now VLAI) to create a spin-off company based on the poly(2-oxazoline) platform. He developed and patented scalable processes for the production of high-quality poly(2-oxazoline)s, with a special focus on biomedical applications. He is co-inventor in several patents and has co-authored more than 20 scientific publications, mostly in the poly(2-oxazoline)s field. Early 2018, Victor co-founded the spin-off company Avroxa bvba, dedicated to the design and production of poly(2-oxazoline)s under the Ultroxa brand name. Victor currently leads a team dedicated to poly(2-oxazoline) applied research and production, being responsible for the operations and R&D activities of Avroxa. Richard Hoogenboom Richard Hoogenboom studied chemical engineering at the Eindhoven University of Technology (TU/e; etherlands). In 2005, he obtained his PhD under the supervision of Ulrich S. Schubert (TU/e) and continued working as project leader for the Dutch Polymer Institute; partly combined with a parttime position as Senior Product Developer at Dolphys Medical. After postdoctoral training with Martin Möller at the RWTH Aachen (Humboldt fellowship; 2008) and Roeland J. M. olte at the Radboud University ijmegen (W veni-grant; 2009), he was appointed as associate professor at Ghent University in 2010 and promoted to full professor in His research interests include poly(2-oxazoline)s, stimuli-responsive polymers, and supramolecular materials, fields in which he is (co)inventor in more than 10 patent families and has co-authored over 300 scientific publications. He is currently associate editor for European Polymer Journal and Australian Journal of Chemistry. 9

10 TCI メール 2019 年夏号 l o. 181 化学よもやま話 ~ 研究室訪問記 ~ 科学クラブを訪ねて 第 36 回化学クラブ研究発表会 (15 ) BZ BZ Blelousov-Zhabotinsky TCI Ru(II) BZ - ph ( - ) DDS ph 1.0~5.5 ph - - ph 10

11 o. 181 l 2019 年夏号 TCI メール Belousov-Zhabotinsky TCI o BG A ,600 ( ) Web 11

12 TCI メール 2019 年夏号 l o. 181 製品紹介 有機合成に使用できる金属ナトリウム分散体 SD Super Fine TM (Sodium 25wt% dispersion in mineral oil) (1) 製品コード : D5792 5g 4,0 円 25g 9,800 円 100g 29,800 円 SD Super Fine TM 1 PCB Bouveault Blanc 1) 2) 1 3) - (Scheme 1) 1 atmp 2 2 4) (Scheme 2) 2 Wittig 1 THF 5) Scheme 1 Preparation of organosodium compounds using 1 and its application to cross-coupling reactions Scheme 2 Preparation of atmp using 1 * 文献 1 J. An, D.. Work, C. Kenyon, D. J. Procter, J. rg. Chem. 2014, 79, ) B. Zhang, H. Li, Y. Ding, Y. Yan, J. An, J. rg. Chem. 2018, 83, ) S. Asako, H. akajima, K. Takai, at. Catal. 2019, 2, ) S. Asako, M. Kodera, H. akajima, K. Takai, Adv. Synth. Catal. 2019, 361, ) R. Inoue, M. Yamaguchi, Y. Murakami, K. kano, A. Mori, ACS mega 2018, 3, 関連製品 ZnCl 2 -TMEDA 25g 13,700 D4393 2,2,6,6-Tetramethylpiperidine 25mL 12,200 2mL 69,200 T1051,,','-Tetramethylethylenediamine (TMEDA) 25mL 1, mL 3,600 0mL 8,300 T0147 Isoprene (stabilized with TBC) 25mL 2,000 0mL 4,0 I 0160 Chlorobenzene 0g 1,600 C

13 o. 181 l 2019 年夏号 TCI メール 骨芽細胞の分化を促進する低分子化合物 (TH) TH (1) 製品コード : M mg 16,000 円 mg 56,000 円 TH (1) 1) 1 2,3) 4,5) 6) 1 文献 1) hba, U.-i. Chung, et al., Biochem. Biophys. Res. Commun. 2007, 357, ) K. akajima, U.-i. Chung, et al., Biochem. Biophys. Res. Commun. 2010, 395, 2. 3) Y. Maeda, S. hba, et al., Biomaterials 2013, 34, ) K. Kanke, S. hba, et al., Stem Cell Reports 2014, 2, ) D. Zujur, S. hba, et al., Sci. Adv. 2017, 3, e ) Y. Fujii, D. Chikazu, et al., Stem Cell Res. Ther. 2018, 9, 自然界に少量しか存在しない四炭糖 D-Erythrose (ca. 70% in Water) (1) D-Threose (contains 35% Water at maximum) (2) 製品コード : E mg 3,0 円 1g 10,400 円製品コード : T mg 11,000 円 1g 38,0 円 D- (1) D- (2) 4 1 D- -4- (4EP) 1) 1 2) 2 3) 文献 1) H. H. Hiatt, B. L. Horecker, J. Bacteriol. 1956, 71, ) L.-L. Liu, T. Yi, X. Zhao, ncol. Lett. 2015, 9, ) J. M. H. Stoop, W. S. Chilton, D. M. Pharr, Phytochemistry 1996, 43, 関連製品 meso-erythritol 25g 6, g 17,800 0g 56,0 E

14 TCI メール 2019 年夏号 l o. 181 SIRT2 阻害剤 AGK-2 (1) 製品コード : A3193 5mg 8,400 円 25mg 29,200 円 100mg 87,0 円 1 2 (SIRT2) HDAC AGK-2 1 SIRT2 3.5 mm IC SIRT1 SIRT3 40 mm a- 文献 1) T. F. uteiro, E. Kontopoulos, S. M. Altmann, I. Kufareva, K. E. Strathearn, A. M. Amore, C. B. Volk, M. M. Maxwell, J.-C. Rochet, P. J. McLean, A. B. Young, R. Abagyan, M. B. Feany, B. T. Hyman, A. G. Kazantsev, Science 2007, 317, 516. SIRT1 および 2 阻害剤 Cambinol (1) 製品コード : C3535 5mg 18,000 円 25mg 63,000 円 1 1 SIRT 1 2 1) SIRT 1 2 AD H4 1 IC 56 mm 59 mm AD 1 2 Ki 7 mm 2) 1 SC 文献 1) B. Heltweg, T. Gatbonton, A. D. Schuler, J. Posakony, H. Li, S. Goehle, R. Kollipara, R. A. DePinho, Y. Gu, J. A. Simon, A. Bedalov, Cancer Res. 2006, 66, ) M. Figuera-Losada, M. Stathis, J. M. Dorskind, A. G. Thomas, V. V. R. Bandaru, S.-W. Yoo,. J. Westwood, G. W. Rogers, J. C. McArthur,. J. Haughey, B. S. Slusher, C. Rojas, PloS E 2015, 10, e

15 o. 181 l 2019 年夏号 TCI メール CASA 試薬 : 新しいキラル MR シフト試薬 (R,R)-CASA-H (1) (S,S)-CASA-H (2) (R,R)-CASA-a (3) (S,S)-CASA-a (4) 製品コード : C mg 6,900 円製品コード : C mg 6,900 円製品コード : C mg 6,900 円製品コード : C mg 6,900 円 CASA 1-4 MR CASA MR 1 1-Phenylethylamine MR 400 MHz CD 3 D S R 文献 1) M.-S. Seo, H. Kim, J. Am. Chem. Soc. 2015, 137, ) M.-S. Seo, S. Jang, H. Kim, Chem. Commun. 2018, 54,

16 TCI メール 2019 年夏号 l o. 181 出展のご案内 < ぜひお立ち寄りください > 第 92 回日本生化学会大会 開催日 :2019 年 9 月 18 日 ( 水 ) ~ 20 日 ( 金 ) 会場 : パシフィコ横浜 第 14 回アジア最先端有機化学国際会議 (ICCECA-14) 開催日 :2019 年 9 月 26 日 ( 木 ) ~ 29 日 ( 日 ) 会場 : ヒルトンニセコビレッジ ( 北海道 ) 第 80 回応用物理学会秋季学術講演会開催日 :2019 年 9 月 18 日 ( 水 )~ 21 日 ( 土 ) 会場 : 北海道大学札幌キャンパス 第 11 回プロテオグリカン国際会議開催日 :2019 年 9 月 29 日 ( 日 )~ 10 月 3 日 ( 木 ) 会場 : 石川県立音楽堂邦楽ホールならびに交流ホール 第 78 回日本癌学会学術総会 開催日 :2019 年 9 月 26 日 ( 木 ) ~ 28 日 ( 土 ) 会場 : 国立京都国際会館 第 45 回反応と合成の進歩シンポジウム 開催日 :2019 年 10 月 28 日 ( 月 ) ~ 29 日 ( 火 ) 会場 : 倉敷市芸文館 ( 岡山 ) 本文に掲載した化学品は試薬であり, 試験 研究用のみに使用するものです 化学知識のある専門家以外の方のご使用はお避けください 弊社は掲載した製品について発生した特許法上の諸問題をユーザーの方々に保証するものではありません 掲載した製品およびその価格等は発行時のものです 諸事情によりやむを得ず変更を行う場合があります 本誌の内容の一部または全部を無断で転載あるいは複製することはご遠慮ください Printed in Japan