著者

綿引 智成

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア

巻号頁・発行日

vol.52, no.9, pp.850-854, 2016

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大麻草を乾燥または樹脂化した大麻には,カンナビノイド(CB)と呼ばれる60種類以上の活性成分が含まれ,古来より鎮痛や食欲増進等の目的で使用されてきた.しかし,陶酔感,短期の記憶・認識障害,または起立性低血圧を引き起こし,さらには依存性リスクも有することから,一部の国や州を除き大麻の医療目的使用は禁止されている.<br>一方,1960年代に,大麻の主活性成分がΔ⁹-テトラヒドロカンナビノール(tetrahydrocannabinol:THC)であることが報告され,1990年代にはTHCの生体内標的分子としてカンナビノイド受容体タイプ1およびタイプ2(cannabinoid receptor type I and type II:CB₁ and CB₂)が同定された.さらに,CB受容体に対する生体内アゴニストとしてアナンダミド(anandamide:AEA)および2-アラキドノイルグリセロール(2-arachidonoylglycerol:2-AG)が発見され,それらに対する主要分解酵素がそれぞれ脂肪酸アミド加水分解酵素(fatty acid amide hydrolase:FAAH)およびモノアシルグリセロールリパーゼ(monoacylglycerol lipase:MAGL)であることも明らかとなっている(図1).<br>本稿では,これらカンナビノイド系分子を標的とした医薬品開発状況を,各種データベースおよび文献情報からまとめたので概説する(表1).

著者

竹越 敏夫

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.20, no.4, pp.332-333, 1984

著者

清水 万紀子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.129, no.11, pp.1351-1356, 2009 (Released:2009-11-01)

参考文献数

23

被引用文献数

1 2

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Individual differences of drug-metabolizing enzymes are important determinants for the metabolic fate of chemicals. This article focuses on polymorphic human flavin-containing monooxygenase 3 (FMO3) and dietary-derived trimethylamine. Malodorous trimethylamine is generally converted to odorless trimethylamine N-oxide by liver microsomal FMO3. Trimethylaminuria is caused by functional disorder of FMO3. In this study mutations of the FMO3 gene were examined in self-reported Japanese trimethylaminuria subjects that showed low FMO3 metabolic capacity in urine tests. Nine novel polymorphisms in the FMO3 gene were discovered in self-reported Japanese volunteers. Functional analyses of recombinant FMO3 proteins suggested that these FMO3 gene mutations were one of the causal factors for decreased FMO3 function resulting in trimethylaminuria. Inter-individual variations of FMO3-mediated microsomal oxygenation activities, levels of FMO3 protein and FMO3 mRNA, and its modification in liver microsomes from Japanese samples were observed. Both genetic polymorphisms in the 5′-upstream of the FMO3 gene and some hormonal changes related to menstruation may be causal factors for inter- and/or intra- individual expression levels of FMO3. To assess the palliative cares, it was found that absorbed levels of trimethylamine in vivo would be possibly controlled by selection of precursor foods like fish containing a variety of trimethylamine amounts. These lines of evidence suggest that individual differences of FMO3 are important determinants for the metabolic fate of dietary-derived trimethylamine.

著者

大野 忠夫

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.53, no.1, pp.1-1, 2017 (Released:2017-01-01)

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2016年7月1日,筆者は知り合いの医師から「オプジーボは,処方医師に専門医資格を求められるなど,未だ使用にハードルが高い薬であるため,自由診療であっても,あるいは自由診療だからこそ,今回の適用外使用は見合わせよう,ということになりました.」というメールを受け取った.直前の6月4日にシカゴで開催された米国臨床腫瘍学会(American Society of Clinical Oncology:ASCO)では(ASCOの間はがんにかかるな,という冗談があるほど,全米のがん治療医が参加する主要学会),オプジーボのような抗体医薬によるがん免疫療法は,もはや臨床現場でも選択肢の1つとして当たり前の治療法になっており,既に話題のピークを過ぎていた.本抗体の劇的な効果がもともとは国内(京都大学)で発見されたにもかかわらず,がん治療の臨床現場レベルになると,我が国は遅れをとってしまっている.既に,「抗PD-1抗体(ペムブロリズマブ)がPD-L1高発現の進行性非小細胞肺がん患者に対するファーストライン治療として,無増悪生存期間および全生存期間において化学療法に対する優越性を示す」(2016年6月28日,https://bio.nikkeibp.co.jp/atcl/release/16/06/28/02114/)という現実が目の前に来ているのだが・・・.日本でもまもなく,「ファーストラインでがん免疫療法を行う」という意味を,医師は患者に説明しなければならなくなるであろう.しかし周知のように,がん免疫療法は手術・放射線・抗がん剤に継ぐ第4の治療法と期待されながら,実際には大学病院も含めて国内のごく普通の臨床現場では,未だに「まだ分からない治療法」なのである.すなわち,国内で承認済みの免疫チェックポイント阻害剤にとどまらず,身体に広く影響が及ぶがん免疫療法の真の意義については,我が国ではごく一部の専門医を除けば,臨床現場におけるほとんどのがん治療医がまだ理解していないのである.まして,医師の処方せんをチェックする薬剤師ではどうかと言えば,(少なくとも本稿執筆時点では)全員素人だと言われても仕方がない状況なのではないか.がん化学療法とがん免疫療法の関係で言えば,「まず抗がん剤治療ありき」から,「最初からがん免疫療法を実施する(これまでの抗がん剤治療に先んじて)」へ,優先順位が逆転するという,いまや常識のコペルニクス的大転換の時代に入っているのである.また,我が国では高齢化に伴ってがん患者は増える一方であり,既に年間37万人ものがん死者がいる.だからこそ,猛烈なスピードで進化しつつあるがん治療法(特にがん免疫療法)について,ファルマシアの読者にはぜひ勉強してもらいたいと願っている.少しでも勉強すれば,誰でもがん治療の臨床現場で最先端の知識を身につけられるのである.時代に置いてけぼりにされるより,はるかに面白いのではなかろうか.

著者

高橋 典子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.122, no.8, pp.547-563, 2002-08-01 (Released:2003-02-18)

参考文献数

79

被引用文献数

4 4

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Cell differentiation is essential for normal growth and homeostasis, and drug-induced differentiation of tumor cells into benign or normal cells is an important approach for anticancer chemotherapy. Studies of induction mechanisms for cell differentiation and discovery of differentiation-inducing factors are thus critical components of drug development. The Screening of differentiation-inducing factors, such as purified aldehyde reductase, a xenobiotic metabolite enzyme, that induces differentiation of human acute myeloid leukemia HL60 cells into monocyte/macrophage cells is described. Mechanisms of all-trans-retinoic acid (RA)-induced differentiation are also covered. RA is a potent inducer of HL60 cell differentiation and when used as a sole agent it can induce complete remission in patients with acute promyelocytic leukemia (APL). While one mechanism of the effect of RA involves RA nuclear receptors, retinoylation (a posttranslational modification of proteins by RA) may be a new nongenomic mechanism by which RA acts on cells. An early event in RA-induced differentiation may be retinoylation of RIIα (regulatory subunits of cAMP-dependent protein kinase), in which RIIα units are retinoylated and the retinoylated RIIα is then translocated to the nucleus. Drugs can also be combined with RA in RA-differentiation therapy. Cytodifferation therapy by RA in APL patients exhibits limitations due to the resistance of relapsed patients to further RA treatment. This may occur through the induction of expression of various genes that reduce RA blood concentrations. Treatment with combinations of RA and other agents may be one way to reduce induction of those genes. Good candidates for such agents include cAMP-elevating agents, retinoids, steroids, and fatty acids that synergistically induce differentiation of HL60 cells. Two derivatives of falconensone A, falconensone A p-bromophenylhydrazone, which has a bromophenyl residue, and falconensone A dioxime, which possesses a hydroxy residue, were synthesized to incorporate features of RA and N-[4-hydroxyphenyl]retinamide. Both derivatives have exhibited more potent biological activity than the parent falconensone A in vitro and in vivo.

著者

伊藤 豊 矢野 真吾 渡辺 和夫 山中 悦二 相見 則郎 坂井 進一郎

出版者

公益社団法人 日本薬学会

雑誌

CHEMICAL & PHARMACEUTICAL BULLETIN (ISSN:00092363)

巻号頁・発行日

vol.38, no.6, pp.1702-1706, 1990

被引用文献数

18

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We investigated the selectivities and structure requirements for alpha-1 and alpha-2 adrenoceptor blocking activities of yohimbine (YO) and its 12 related analogs, such as &beta;-yohimbine (&beta;-YO), dihydrocorynantheine (DHC) and (-)indoloquinolizidine ((-)IQ). The affinity of YO analogs to alpha-adrenoceptor was assessed by measuring their blockade of pressor responses to epinephrine in pithed rats. Among YO structure groups, the potency order was YO>DHC=&beta;-YO>geissoschizine methylether>14&beta;-hydroxy YO>14&beta;-benzoyloxy YO (inactive). (-)IQ was slightly less potent than YO, but much stronger than (+)IQ. Among (&plusmn;)IQ structure groups, the potency order was (&plusmn;)IQ>(&plusmn;)1, 12b-trans-1-hydroxy IQ&raquo;(&plusmn;)1, 12b-cis-1-hydroxy IQ (imactive). (&plusmn;)Borrerine was active, but (&plusmn;)desmethylborrerine was inactive. The alpha-1 blocking activities of the four compounds YO, &beta;-YO, DHC and (-)IQ, were assessed in experiments of pressor responses to methoxamine in pithed rats and contractile responses to methoxamine in the rat vas deferens. The potency order was (-)IQ>YO>DHC>&beta;-YO. Furthermore, the alpha-2 blocking activities of the four analogs were assessed in experiments of pressor responses to clonidine and inhibition of electrically driven cardioacceleration by clonidine, in pithed rats. The potency order was YO>&beta;-YO>(-)IQ>DHC. Based on the potency ratio between alpha-1 and alpha-2 blocking activities, DHC or YO was most selective for alpha-1 or alpha-2 subtype, respectively, among the four YO analogs. These results suggest that the A, B, C and D rings of YO analogs and their planarity are necessary for the affinity to alpha-adrenoceptors and that the predominant conformation of the carboxymethyl or hydroxy group on the E ring of YO structure determines the selectivity for alpha-1 and alpha-2 blocking activities.

著者

猪熊 翼 佐藤 伸一

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.138, no.1, pp.37-38, 2018 (Released:2018-01-01)

著者

落合 英二 小林 五郎 林 英作 野口 雄一郎

出版者

公益社団法人 日本薬学会

雑誌

薬学雑誌. 乙号 (ISSN:00316903)

巻号頁・発行日

vol.66, no.7-12, pp.78-81, 1953-10-25 (Released:2009-10-22)

参考文献数

5

著者

寺町 ひとみ 杉田 郁人 伊野 陽子 林 勇汰 吉田 阿希 大坪 愛実 上野 杏莉 勝野 隼人 野口 義紘 井口 和弘 舘 知也

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.137, no.9, pp.1177-1184, 2017 (Released:2017-09-01)

参考文献数

21

被引用文献数

4

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We analyzed impression data and the scale of communication skills of students using text mining method to clarify which area a student was conscious of in communication in practical training. The results revealed that students tended to be conscious of the difference between practical hospital training and practical pharmacy training. In practical hospital training, specific expressions denoting relationships were “patient-visit”, “counseling-conduct”, “patient-counseling”, and “patient-talk”. In practical pharmacy training, specific expressions denoting relationships were “patient counseling-conduct”, “story-listen”, “patient-many”, and “patient-visit”. In practical hospital training, the word “patient” was connected to many words suggesting that students were conscious of a patient-centered communication. In practical pharmacy training, words such as “patient counseling”, “patient”, and “explanation” were placed in center and connected with many other words and there was an independent relationship between “communication” and “accept”. In conclusion, it was suggested that students attempted active patient-centered communication in practical hospital training, while they were conscious of listening closely in patient counseling in practical pharmacy training.

著者

山野 喜昭 池谷 理 大前 雅彦 河部 靖

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.99, no.11, pp.1102-1110, 1979-11-25 (Released:2008-05-30)

参考文献数

8

被引用文献数

2 8

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In order to study cis-trans photo-isomerization of phylloquinone (K) and menaquinone-4 (MK-4), a high-performance liquid chromatographic method for the determination of cis-trans isomers was developed. After removal of the surface active agent and photo-decomposition products, cis-trans isomers were separated on a Nucleosil 50 (particle size ; 5 μm) column using di-n-butyl ether-n-hexane (6 : 94) as a mobile phase. The internal standards used were MK-4 for K and K for MK-4. When either cis or trans compound of K and MK-4 were photo-irradiated in benzene, cis&rlhar;trans photo-isomerization was observed and an equilibrium favoring the trans isomers was attained. Trans→cis photo-isomerization of MK-4 was also observed in injection and in infusion solution. Photo-isomerization and photolysis in their solution were inhibited considerably by using a light-intercepting shade.

著者

宮崎 正三 堀 了平 有田 隆一

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.95, no.6, pp.629-633, 1975-06-25 (Released:2008-05-30)

参考文献数

14

被引用文献数

2 6

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Four different solid phases of tetracycline (trihydrate, anhydrate, dehydrate, and amorphous) were isolated. These phases were characterized by using IR spectroscopy, X-ray powder diffraction, and thermogravimetric and differential thermal analyses. Dissolution behavior of these phases in distilled water was investigated and an appreciable difference in the dissolution behavior was detected between the amorphous and the other solid phases. The effect of the solid phases on bioavailability of tetracycline was also studied. Blood plasma levels obtained in rabbits and blood levels in rats after intraduodenal administration of the trihydrate and amorphous were compared, and its results indicated that the solubility difference between the two phases has an effect on the bioavailability of tetracycline. The cumulative excretion of tetracyc1ine in urine after oral administration of the two phases to human subjects was also examined and its results indicated that the cumulative amount after administration of the amorphous was slightly higher than that of the trihydrate.

著者

湯浅 龍三 今井 淳 森川 裕司 草嶋 久生 内田 広 入倉 勉

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.102, no.5, pp.469-476, 1982-05-25 (Released:2008-05-30)

参考文献数

9

被引用文献数

2 6

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The presence of three kinds of hydrates of AM-715 (1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid) was confirmed by elemental analysis, Karl-Fischer method, thermogravimetric analysis, differential scanning calorimetry, infrared spectroscopy, and X-ray diffractometry. Anhydrous AM-715 was not hygroscopic under less than 36% of relative humidity, but easily transformed to 5/2-hydrate over 62-78% of relative humidity and 5-hydrate above 94% of relative humidity, at 40°C. Anhydrous AM-715 was transformed to 5/2-hydrate with the first-order kinetics and 5/2-hydrate was dehydrated according to the first-order kinetics with an activation energy of dehydration of 22 kcal/mol. The 5/2-hydrate was converted to 5-hydrate much slowly than anhydrous AM-715. Dissolution rates were determined in water by using tape procedure, showing a slight difference between anhydrous AM-715 and its hydrates. In order to determine the effect of hydration on bioavailability, the serum levels in dogs were measured after oral administration. There were no significant differences among bioavailability of anhydrous AM-715, its 5/2-hydrate and 5-hydrate.

著者

國友 勝

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.127, no.12, pp.1997-2014, 2007 (Released:2007-12-01)

参考文献数

108

被引用文献数

16 26

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Oxidative stress is a continuous level of oxidative damage in animal cells, which is caused by an overabundance of reactive oxygen species or a decline in antioxidant ability against them. Oxidative stress increases with individual risk factors of atherosclerosis such as obesity, hypertension, hyperlipidemia, diabetes and smoking. Thus, oxidative stress is considered to play a key role in the pathogenesis of atherosclerosis. This review discusses the relationship between oxidative stress and atherosclerosis based on findings from our research group. We have found that atherosclerotic lesions are formed in the aorta of mice fed a high-cholesterol and high-linoleic diet, in parallel with elevated serum lipid peroxide levels. This model is useful for primary screening of antiatherosclerotic agents with antioxidative activity. One notable factor in the development of atherosclerosis is oxidized low-density lipoprotein (OxLDL). In order to examine OxLDL levels in blood, we have developed anion-exchange HPLC methods using stepwise elution. Using these methods, we have found that OxLDL markedly increases in a rat model of metabolic syndrome, in animals exposed to cigarette smoke and in smokers in parallel with other oxidative stress markers. These oxidative stress markers have been attenuated by administration of several antioxidants. In addition, we have found that smoking accelerates atherogenesis in the aorta of apoE-deficient mice and this acceleration can be ameliorated by administration of vitamin E. These observations suggest that antioxidant supplementation may be an effective therapeutic strategy for metabolic syndrome and smoking-induced diseases in which elevated oxidative stress plays a pivotal role.

著者

粟田 則男 山本 恵一 中川 寛 杉本 功 坂田 英彦 佐藤 久

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.99, no.2, pp.141-145, 1979-02-25 (Released:2008-05-30)

参考文献数

11

被引用文献数

1 2

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Acebutolol hydrochloride was proved by thermal analysis (DTA and TG), IR spectra, and X-ray powder diffraction to have three crystalline forms (form I, II, and III) and an amorphous form. The amorphous form, which was stored at 20°under 91% R.H., was first transformed to forms II and III, and then it was finally transformed to form I. During this transformation, the incorporation and release of water were examined. Form I was stable at this condition, while form II was transformed to form I for 48 hr, and form III was transformed to form I for 2 hr. Further, it was found that the amorphous form was transformed to form II at 80°under 50% R.H. for 3 hr, but at 80°under vacuum it was transformed to form III. Form I at 138°for 8 hr and form III at 130°for 4 hr were transformed to form II. From these results it was concluded that form I was the most stable form at room temperature.

著者

岡田 芳男

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.129, no.10, pp.1141-1154, 2009 (Released:2009-10-01)

参考文献数

36

被引用文献数

3 5

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This review documents my research for the past 45 years in peptide chemistry. Initially, in order to study the structure-activity relationships of active center of α- and β-melanocyte stimulating hormones (H-His-Phe-Arg-Trp-Gly-OH), we employed D-amino acids. That approach yielded first published report in 1965 of antagonists containing D-amino acids. Monkey β-melanocyte stimulating hormone (β-MSH), an 18 amino acid peptide stimulated pigment cells. We synthesized β-MSH and fragments thereof, and studied in detail structure-activity relationships. A major and valuable result revealed that the C-terminal pentadecapeptide of β-MSH exhibited higher MSH activity than the parent hormone providing a new question; namely, what was the role of the N-terminal tripeptide? In order to identify the novel enzyme, spleen fibrinolytic proteinase (SFP), I developed a specific chromogenic substrate, Suc-Ala-Tyr-Leu-Val-pNA, and a specific inhibitor, Suc-Tyr-D-Leu-D-Val-pNA, once again employing my D-amino acid strategy. SFP was purified by affinity chromatography using Suc-Tyr-D-Leu-D-Val-pNA as the bound ligand. The success of this approach provided me the incentive to develop a variety of potential drugs. Thus, I prepared a specific plasmin inhibitor (YO-2) and a plasma kallikrein inhibitor (PKSI-527). Next, my research developed novel opioid receptor specific opioid agonists and antagonists based on 2′,6′-dimethyl-L-tyrosine (Dmt) dimers coupled with unique pyrazinone ring as a spacer. They exhibited potent oral antinociceptive activity acting through the μ-opioid receptor. Potent μ-receptor agonists (H-Dmt-Pro-Phe/Trp- Phe-NH2) were transformed into highly selective μ-receptor antagonists (N-allyl-Dmt-Pro-Phe/Trp-Phe-NH2), which reversed ethanol-induced increases in GABAergic neurotransmission, suggesting the possibility that they may emerge as candidates for the treatment of ethanol addiction.

著者

宮田 興子

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.53, no.12, pp.1198-1198, 2017 (Released:2017-12-01)

参考文献数

1

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6年制薬学部において、有機化学は医薬品をとりまく臨床現場での話題や問題を理解し、解決するための手段として利用すべき科目の一つである。今回、薬剤師国家試験にも取り上げられている大腸がん治療法、FOLFIRIおよびFOLFOX療法に焦点をあてて、この療法を有機化学的に理解するためにはどのような有機化学反応を理解している必要があるかを示して、医療における有機化学力の活用法の一つを示す。

著者

萬代 大樹

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.52, no.5, pp.434-434, 2016 (Released:2016-05-01)

参考文献数

3

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近年,有機分子触媒の分野は著しい発展を遂げており,遷移金属触媒と並ぶ重要な研究分野となっている.しかし,高いターンオーバー数(TON)あるいはターンオーバー頻度(TOF)を示す高活性有機分子触媒はいまだ報告例が少ないのが実情である.Songらは,100ppm(=0.01mol%)以下の触媒量でもシリル化による第二級アルコールの速度論的光学分割反応が円滑に進行することを見いだしたので,本稿で紹介する.なお,本稿は下記の文献に基づいて,その研究成果を紹介するものである.1) Müller C. E., Schreiner P. R., Angew. Chem. Int. Ed. Engl., 50, 6012-6042 (2011).2) Park S. Y. et al., Nat. Commun., online 18 Jun. 2015, doi : 10.1038/ncomms8512.3) Zhao Y. et al., Nature, 443, 67-70 (2006).

著者

平沼 英敏

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.39, no.8, pp.753-757, 2003

参考文献数

9

著者

中上 博秋

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.39, no.3, pp.204-208, 2003

著者

国嶋 崇隆

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.128, no.3, pp.425-438, 2008 (Released:2008-03-01)

参考文献数

40

被引用文献数

1 3

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Reaction rates and selectivities can be critically affected by the reaction field. Using a diverse set of reagents and reaction systems, the author reviews a variety of ways to control the reaction field. In the first example, we discuss 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), which serves as an exceptionally convenient reagent for dehydrocondensation. In particular, formation of carboxamide by DMT-MM was found to take place even if water or alcohol were used as a reaction medium. Thus, chemical modification of carboxyl groups and/or amino groups of highly polar substrates, such as amino acid derivatives, peptides, glyco-chains, and nucleotides, can be simply effected by mixing them with DMT-MM in aqueous or alcoholic solvents. The author also found that a tertiary amine catalyzes the activation step of carboxylic acid with 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) via in situ generation of coupling reagents. Proceeding further in this direction, we determined that artificial acyltransferase and cyclotransferase could be formed by conjugation of a tertiary amine catalyst to host-molecules to mimic a substrate binding site. Finally, the micellar interface, well known for promoting hydrolysis, clearly provides a superior reaction field for dehydrocondensation. When a 1,3,5-triazine-type amphiphilic dehydrocondensing agent was used, bimolecular dehydrocondensation between amphiphilic carboxylate and amines was highly accelerated (2000-fold) in a micellar system. Spontaneous membrane fusion was induced by adoption of the micellar reaction in the ceramide synthesis at the surface of membranes. All together, these diverse findings strongly support the central importance of the reaction field in controlling reaction rates and selectivity.