Signal transduction, a step forward in medicine regarding regulators of cellular process.
First phospholipid was reported from bovine brain Brockenhoff in 1961 . The findingwas followed by the hypothesis that the receptor controlled hydrolysis of phosphoinositides could be directly linked to cellular calcium mobilization of Michell in 1975 . The discovery by Berridge found that D--myo-inositol 1,4,5-trisphosphate([IP.sub.3]) act as a second messenger, and the fundamental cell-signal transduction mechanism has been elucidated. [IP.sub.3] stimulates the release of [Ca.sup.2+] from the intracellular stores in the endoplasmic reticulum through [IP.sub.3] receptor while regulating a wide range of cellular processes [3-27].
Ozaki et al.  succeeded in the first total synthesis of optically active my-inositol trisphosphate involving 13 stepsi from readily available myo-inositol [28,29]. Later on several IPx and phosphinositide (PIPx) were synthesized by developing differentsynthetic methods and new reagents.
Inositol is actually a vitamin like compound found in both plants and animals. Plants are known to produce inositol from glucose and make PIPx from inositol for signal transduction [25,26]. The synthesis of other important reagents is defined as follow.
Synthetic Competition of Inositol Phosphates
The synthesis of I (1,4,5) [P.sub.3] from inositol orthoformate, Vacca , from myo-inositol , from arens using Pseudomonus oxidation Ley  from Quinic acid, Falck  from inositol, Stephanov  Phosphothioate analogues Potter 
Maracekand Prestwich [36,37] prepared D-myo-(3H)I [P.sub.3] (1,4,5), essential and most used reagent for the study of signal transduction.
Preparation of IPx, [IP.sub.3] Derivatives, [IP.sub.3] Analogues and Assessment of their Activities
Several compounds were synthesized and tested in our laboratory for making advances in signal transduction studies [38-86]. Such efforts included supply of necessary reagents such as [IP.sub.3], other IPX used to such investigations. Furthermore the finding included the new methods of synthesis and development of reagents described. However, details were described in our earlier review article on transdution [38-41].
Inositol phosphate I[P.sub.x]
4-glucopyranosyl inositol, 1-tartaric acid derivative  enzyme aided inositol derivative , 1,3,5-tribenboyl-inositol , Inositol monophosphate IPIP(1) [43,45,46]; Inositol bisphophate IP2-IP2(5,6) , IP2(3,4) ; Inositol tris phosphateIP3-IP3(1,4,5) [44,48-50,45-65],IP3(1,4,5) analogue [57-63,64], IP3(1,3,4) , IP3(2,4,5) [45,65], IP3 (3,4,5) [58,66,67] IP3(2,4,5) [51,55],IP3(1,4,6) IP3(1,4,6) , IP3(1,3,4) , IP3(1,2-cyclic 4,5 [47,54], IP3(1,4,5) phsphofluoridate [62,63],unsaturated IP3(3,4,5) .
2-substituted IP3 (1,4,5) [57-59], 3-Substituted IP3 [60,67]
Inositol tetrakis phosphateIP4
IP4(1,3,4,5) [50,58,59,63,68),IP4(1,3,4,6) [47,63], IP4(1,4,5,6) , PI4(1,2,5,6) [68,69]
IP4(3,4,5,6) [67,68],IP4(1,3,4,5)analogues [63,70-72]
IP4(1,2,4,5) analogues 
Inositol pentakis phosphate IP5
Phosphoinositide PIPx 
In addition, many Inositol lipid, Phosphatidyl inositol, PIPx [72-76]. Our efforts also lead to develop phosphonium salt methodology [39,77] and other compounds summarized as follows:
* Phosphatidyinositol 3,4,5-trisphosphate 
* Stearoyl-linolenoyl-PI(3,4,5)[P.sub.3] 
* Unsaturatedl-PI(3,4,5)[P.sub.3] 
* 2,6-Di-O-(D- mannopyranosyl)phosphatidyl-D-myo-inositol 
It is worth mentioning that 2-Substituted IP3 analogues were also synthesized which were used for the preparation of affinity columns. The reaction of 2-aminobenzoyl-inosl1,4,5-trisphosphate with affinity resin gave IP3 affinity column. Using this affinity resin, we could get IP3-binding protein, and such proteins were characterized .
* Putative inositol 1,4,5-trisphosphate binding protein in rat brain cytozol .
* Partial purification and reconstitution of inositol 1,4,5-trisphosphate receptor/calcium channel of bovine liver microsomes .
* Inositol 1,4,5-triphosphate Affinity Chromatography. Fishing out Ins(1,4,5) [P.sub.3]-recognizable Protein .
* Inositol 1,4,5-trisphosphate binding to porcine tracheal smooth muscle aldolase .
* A new inositol 1,4,5-trisphosphate binding protein similar to phospholipase C-d 1 .
* D-myo-Inositol 1,4,5-trisphosphate-binding proteins in rat brain membranes .
* Expression and characterization of an inositol 1,4,5-trisphosphate binding domain of phosphatidylinositol-specific phospholipase CD1 .
* D-myo-Inositol 1,4,5-trisphosphate binding domain of phospholipase CD 1 .
* Platelet-derived growth factor activates protein kinase Ce through redundant and independent signaling pathways involving phospholipase Cg or phosphatidylinositol 3-kinase .
* Detection and partial purification of inositol 1,4,5-trisphosphate 3-kinase from porcine skeletal muscle. Cellular Signallimg .
* The metabolism of D-myo-inositol 1,4,5-trisphosphate and Dmyo-inositol 1,3,4,5-tetrakisphosphate by porcine skeletal muscle .
* Isolation of the active form of RAC-protein kinase (PKB/Akt) from transfected COS-7 cells treated with heat shock stress and effects of phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 4,5-bisphosphate on its enzyme activity .
* Expression and characterization of an inositol 1,4,5-trisphosphate binding domain of phosphatidylinositol-specific phospholipase CD-1 .
* A novel A-isoform-like inositol 1,4,5-trisphosphate 3-kinase from chicken erythrocytes exhibits alternative splicing and conservation of intron positions between vertebrates and invertebrates .
Discovery of Medicine
During of research work, I could discover Carmofur, which is an orally active antitumor agent. HCFU, 1-hexylcarbamoyl-5-fluorouracil [91-94]. This compound was obtained from 5-fluorouracil and hexyl isocyanate . However in the current communication, I wish to describe our successful attempts in developing the compounds related with signal transduction. An ionization property of phosphatydylinositol polyphosphate in mixed model membranes was also reported.
The materials concerning signal transduction are inositol, inositol trisphosphate and G-protein. These compounds are playing very important role for the discovery of new medicines. This is clear from the facts that many investigators working on these materials are highly cited researchers and they were honored with Nobel prizes and Lasker awards.
Inositol is an elegant sweet sugar. The seeds like rice, wheat and corn contain much phytic acid (inositol hexaphosphate) as Ca salt. Plants make glucose by photo synthesis from carbon dioxide and water. Some of the glucose is converted to inositol. Inositol is converted to phospholipids ([PIP.sub.2]) and phytic acid. [PIP.sub.2] is converted to [IP.sub.3] and diacylglycerol. These two compounds are essential for signal transduction of plants. It is well established that plant make phytic acid as a storage of phosphorous. Phosphorous is an essential atom as fertilizer because phosphorous is an essential atom to make nucleic acid, DNA, The seed store phosphorous atom as a store, so that seeds might be able to germinate on land lacking phosphorous.
It is well understood by new that inositol is biosynthesized in plant but seldom produced in animal. Therefore it is classified as an essential carbohydrate which is a kind of vitamin. The anti-oxidant and prooxidant activity of some B-vitamin and vitamin like compounds . Adrabidopain inositol trisphosporter-4 mediates high-affinity [H.sup.+] symport of myo-inositol across the plasma membrane . Inositol is called as a king of biologically active compounds. Inositol is active for anti-hyperlipidemia and called as anti hyperlipidea liver vitamin. Inositol is also active for panic disorder [96,97] and depressive disorder [98,99].
Inositol is produced from rice brain at TsunoShokuhinInd (Wakayama, Japan) in large quantities and used as healthy food, diet food, supplement, healthy drink, dog food, fish food and taste improving material, cosmetic, medicine.
Inositol is converted to phosphoinositides (PIPx) while [PIP.sub.2] is converted to [IP.sub.3] and diacylglycerol. These two compounds are essential for signal transduction. Therefore inositol is used as medicine, health food and health drink.
Berridge and Nishizuka won Albert Lasker Basic Medical Research award and Wolf Prize in Medicine for "their discoveries concerning cellular transmembrane signaling involving phospholipids and calcium.
Seeds and Brian K [100-105] were awarded Chemistry Nobel prize in 2012. They cloned the gene first for the [beta]-adrenergic receptor, and then rapidly thereafter, for a total of 8 adrenergic receptors. This led to the seminal discovery that all GPCRs have a very similar molecular structure. Today we know that about 1,000 receptors in the human body belong to this same family.
Discovery of Regulators of [Ca.sup.2+] release and Consequent Cellular Processes
Since 1997, we were studying 2-aminoethyl diphenylborinate (2-APB) analogues to find IP3 receptor inhibitor and regulate IP3-induced calcium release [106-128].
We discovered that Diphenylaminoacidonate (O,N) borane. (DAB) adducts of amino acid with diphenyl borinic acid are best compounds [129-132].
We think that 911 DiphenylL- lysinate O,N) borane , 919 Diphenyl 2,3-diaminopropionate O,Nborane are the best 2 compounds
[FORMULA NOT REPRODUCIBLE IN ASCII]
911 IC50 0.2
919 IC50 0.2
By choosing the compound we can control the release of [Ca.sup.2+] and regulate many cellular processes such as secretion, cardiac contraction, fertilization, proliferation synaptic plasticity, atrial arryhythmiss , inhibition of calcium entry channel [116,117], excitation-contraction coupling in the heart , arrhythmogenic action of endothelin-1 on ventricular cardiac myocytes [116-122], dysreguration of neural calcium signaling in heart disorders [120-122]. Alzheimer disease [133-139], Huntington aggregation [140-144] and protein cross- link by transglutaminase [140-144].
Recently we found that DAB inhibited Huntington cell aggregation proportionally at SOCE inhibition activity of compounds and Huntington cell aggregation inhibition degree. This is a clear example that DAB regulated the cell response .
The 2-APB analogues presented in this study could be proven to be excellent lead compounds for many human diseases including heart diseases [120,122], Alzheimer's [136-139] and Huntington's disease [140-144].
We found that boron compounds also can inhibit transglutaminase (Ca2+-dependent enzyme) . There are many neurodegenerative disease, including Alzheimer's disease, Huntington's disease. We looked for more effective transglutaminase inhibitors. We synthesized 250 p-aminoethyl ketones and found that these compounds had strong transglutaminase inhibitory activities [143,144]. A typical compound is 5-bromo-2-thienyl-(N-t-butyl-N-benzyl)-aminoethyl ketone.
The boron compounds were found to be effective as inhibitor of acyl protein thioesterase .
I would like to thank Dr. M. J. Berridge and Dr. K.Mikoshiba for valuable suggestions and advices.
[1.] Brockenhoff H, Ballou CE (1961) Phosphate Incorporation in Brain Phosphoinositides. J Biol Chem 236: 49-52.
[2.] Michell RH (1975) Inositol phospholipids and cell surface receptor function. Biochim BiophysActa 415: 81-47.
[3.] Fain JN, Berridge MJ (1979) Relationship between hormonal activation of phosphatidylinositol hydrolysis, fluid secretion and calcium flux in the blowfly salivary gland. Biochem J 178: 45-58.
[4.] Fain JN, Berridge MJ (1979) Relationship between phosphatidylinositol synthesis and recovery of 5-hydroxytryptamine responsive-Ca2+ flux in blowfly salivary gland. Biochem. J 180: 655-661.
[5.] Streb H, Irvine RF, Berridge MJ, Schulz (1983) Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol 1,4,5-trisphosphate. Nature 306 67-69.
[6.] Berridge MJ, Dawson RM, Downes CP, Heslop JP, Irvine RF (1983) Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides. Biochem J 212: 473-482.
[7.] Berridge MJ (1983) Rapid accumulation of inositol trisphosphate reveals that agonists hydrolysepolyphosphoinositides instead of phosphatidylinositol. Biochem. J. 212: 849-858.
[8.] Berridge MJ, Heslop JP, Irvine RF, Brown KD (1984) Inositol trisphosphate formation and calcium mobilization in Swiss 3T3 cells in response to platelet-derived growth factor. Biochem J 222: 195-201.
[9.] Brown JE, Rubin LJ, Ghalayini AJ (1984) A biochemical and electrophysiological examination of myo-inositol polyphosphate as a putative messenger for excitation in Limulus ventral photoreceptor cells. Nature. 311: 160-163.
[10.] Burgess GM, Godfrey PP, McKinney JS, Berridge MJ, Irvine RF, et al. (1984) The second messenger linking receptor activation to internal Ca release in liver. Nature 309: 63-66.
[11.] Prentki M, Biden TJ, Janjic D, Irvine RF, Berridge MJ, et al. (1984) Rapid mobilization of Ca2+ from rat insulinomamicrosomes by inositol-1,4,5-trisphosphate. Nature 309: 562-564.
[12.] Irvine RF, Brown KD, Berridge MJ (1984) Specificity of inositol trisphosphate-induced calcium release from permeabilized Swiss-mouse 3T3 cells. Biochem J 222: 269-272.
[13.] Irvine RF, Letcher AJ, Heslop JP, Berridge MJ (1986) The inositol tris/ tetrakisphosphate pathway--demonstration of Ins(1,4,5)[P.sub.3] 3-kinase activity in animal tissues. Nature 320: 631-634.
[14.] Rapp PE, Berridge MJ (1981) The control of transepithelial potential oscillations in the salivary gland of Calliphoraerythrocephala. Exp Biol 93: 119-132.
[15.] Missiaen L, Taylor CW, Berridge MJ (1991) Spontaneous calcium release from inositol trisphosphate-sensitive calcium stores. Nature 352: 241-244.
[16.] Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312: 315-321.
[17.] Berridge MJ (1987) Inositol trisphosphate and diacylglycerol: two interacting second messengers. Annu Rev Biochem 56: 159-193.
[18.] Berridge MJ, Irvine RF (1989) Inositol phosphates and cell signalling. Nature 341: 197-205.
[19.] Berridge MJ, Downes CP, Hanley MR (1989) Neural and developmental actions of lithium: a unifying hypothesis. Cell 59: 411-419.
[20.] Berridge MJ (1993) Inositol trisphosphate and calcium signalling. Nature 361: 315-325.
[21.] Bootman MD, Berridge MJ (1995) The elemental principles of calcium signaling. Cell 83: 675-678.
[22.] Berridge MJ (1993) Cell signalling. A tale of two messengers. Nature 365: 388-389.
[23.] Decrock E, De Bock M, Wang N, Gadicherla AK, Bol M, et al. (2013) [IP.sub.3], a small molecule with a powerful message. BiochimBiophysActa 1833: 1772-1786.
[24.] Berridge MJ (2009) Inositol trisphosphate and calcium signalling mechanisms. BiochimBiophysActa 1793: 933-940.
[25.] Hu ML, Chen YK, Lin YF (1995) The antioxidant and prooxidant activity of some B vitamins and vitamin-like compounds. ChemBiol Interact 97: 63-73.
[26.] Schneider S, Schneidereit A, Konrad KR, Hajirezaei MR, Gramann M, et al. (2006) Arabidopsis INOSITOL TRANSPORTER4 mediates highaffinity H+ symport of myoinositol across the plasma membrane. Plant Physiol 141: 565-577.
[27.] Kooijman EE, King KE, Gangoda M, Gericke A (2009) Ionization properties of phosphatidylinositol polyphosphates in mixed model membranes. Biochemistry 48: 9360-9371.
[28.] Ozaki S, WatanabeY, Ogasawara T, KondoY, Shiotani N, et al. (1986) Total Synthesis of optically active myo-inositol 1,4,5-trisphosphate. Tetrahedron Letters 27: 3157-3160.
[29.] Ozaki S, KondoY, Shiotani N, Ogasawara T, Watanabe Y (1992) Synthesis and some properties of D-myo-inositol 1,4,5-tris(dihydrogen phosphate). J. Chem. Soc. Perkin Trans. 1: 729-737.
[30.] Vacca IP, Solms JS, Young SD, HuffJ R, Billington DC, et al. (1989) Synthesis of myo-inisitolpolyphoaphates. Tetrahedron 45: 5679-5702.
[31.] Tegge W, Ballou CE(1989) Proc Natl Acad Sci USA 86: 94.
[32.] Ley SV, Parra M, Redgrave AJ, Sterunfeld F (1990) Microbial oxidation in synthesis: preparation of myo-inositol phosphates and related cyclitol derivatives from benzene. Tetrahedro 46: 4995.
[33.] Falck JR, Yadagiri P (1989) Enantiospecific synthesis of D-myo-inositol 1.4.5-trisphosphate from (-)-quinic acid. J.Org.Chem 54: 5851-5852.
[34.] Stepanov AE, Runova OB, Schlewer G, Spiess B, Shvets VI (1989) Total syntheses of chiral sn-myo-inositol-1,4,5-trisphosphate1 and its enantiomer. Tetrahedr Letters 30: 5125-5128.
[35.] Potter BVL (1991) Phosphothioate analogues of D-myo-inositol 1,4,5-Trisphosphate. ACS Symposium Series 463, Inositol polyphosphate and derivatives Edit Allen B.Reitz 186-201.
[36.] Maracek JP, Prestwich GD (1989) Synthesis of tritium-labelled enantiomers of myo-inositol 1,4,5-trisphosphate. J. Labelled comp 27: 917.
[37.] Prestwich GD, Marecek JF (1991) Chemical modification of inositol trisphosphate: Tritiated,fluorinated and phosphate-tetered analogues, ACS Symposium Series 463 Inositol polyphosphate and derivatives Edit Allen B.Reitz 122-131.
[38.] Ozaki, Shoichiro, Watanabe, Yutaka (1991) Synthesis of inositol phosphates and Derivatives ACS Symposium Series 463 Edit. Allen B.Reitz. 41-64
[39.] Ozaki S, Watanabe Y, Takehiro M, Yuichi H; Tomio O, et al. (1998) Synthesis of phosphatidyl-myo-inositol polyphosphates and derivatives. ACS Symposium Series, 718 Phosphoinositides, PP: 212-221.
[40.] Ozaki S (2014) Chemical approach to Signal transduction by inositol trisphosphate J Bioengineer & Biomedical Sci 4:133.
[41.] Shoichiro O, Lei L (1997) Chemoenzymatic Synthesis of Optically Active myo-inositol Polyphosphate. Carbohydrates in Drug Design. Z. J. Witczak (Eds) Marcel Dekker Inc. 343-384.
[42.] Lei L, Ozaki S (1995) Enzymic resolution of the sterically hindered myoinositol derivative. Bulletin of the Chemical Society of Japan 68: 1200-1205.
[43.] Watanabe, Yutaka; Oka, Akinori; Shimizu, Yasushi; Ozaki, Shoichiro (1990) Easy access of optically active myo-inositol derivatives by enantioselective acylation using a tartaric acid monoester. Tetrahedron Letters 31: 2613-2616.
[44.] Akiyama, Takahiko; Takechi, Naoto; Ozaki, Shoichiro. (1990) Chiral synthesis of D-myo-inositol 1-phosphate starting from L-quebrachitol. Tetrahedron Letters 31: 1433-1434.
[45.] Lei L, Ozaki S (1993) Enzyme aided synthesis of D-myo-inositol 1,4,5-trisphospgate. Tetrahedron Letter 34(15) 2501-2504.
[46.] Ling L, Ozaki S (1994) A chemoenzymatic synthesis of D-myo-inositol 1.4.5-trisphosphate. Carbohydr Res 256: 49-58.
[47.] Yutaka W, Tomio O, Hiroyuki H, Tomoko M; Ozaki, Shoichiro.(1988) A versatile intermediate, D-4,5-bis(dibenzylphosphoryl)-myo-inositol derivative, for synthesis of inositol phosphates. Synthesis of 1,2-cyclic-4,5-, 1,4,5-, and 2,4,5-trisphosphate. Tetrahedron Letters 29: 5259-5262.
[48.] Watanabe, Yutaka; Fujimoto, Takahiro; Shinohara, Tomoichi; Ozaki, Shoichiro. (1991) A short step synthesis of optically active myo-inositol 220.127.116.11-tetrakis(phosphate) and myo-inositol 1,4,5-tris(phosphate) from 1.3.5- tri-O-benzoyl-myo-inositol. J Chem Society ChemCommun 6: 428-429.
[49.] Ling L1, Li X, Watanabe Y, Akiyama T, Ozaki S (1993) Enzymatic resolution of racemic 1,2:5,6-di-O-cyclohexylidene and 1,2:3,4-di-O-cyclohexylidene-myo-inositol. Bioorg Med Chem 1: 155-159.
[50.] Yutaka W, Tomio O, Naokazu S, Ozaki S (1987) Stepwise phosphorylation of vicinal diol and sterically hindered alcohol directed toward D-myo-inositol 2,4,5-trisphosphate. Tetrahedron Letters 28: 2607-2610.
[51.] Lei L, Ozaki S (1993) Enzyme aided synthesis of D-myo-inositol 1,4,5-trisphospgate. Tetrahedron Letter 34: 2501-2504.
[52.] Yutaka W, Tomio O, Ozaki S, Masato H (1994) Synthesis of myo-inositol 1.4.6-trisphosphate, an analog of myo-inositol 1,4,5-trisphosphate. Carbohydrate Research 258: 87-92.
[53.] Ozaki S, Masayasu K, Hiroyuki N, Motonobu B, Yutaka W (1988) Synthesis of optically active myo-inositol 1,3,4-trisphosphate. Chemistry Letters 1: 77-80.
[54.] Yutaka W, Tomio O, Hiroyuki N, Tomoko M, Ozaki S (1988) A versatile intermediate, D-4,5-bis(dibenzylphosphoryl)-myo-inositol derivative, for synthesis of inositol phosphates. Synthesis of 1,2-cyclic-4,5-, 1,4,5-, and 2,4,5-trisphosphate. Tetrahedron Letters 29: 5259-62.
[55.] Yutaka W, Nobuyuki H, Ozaki S (1988) Dibenzylphosphorofluoridate, a new phosphorylating agent. Tetrahedron Letters 29: 5763-5764.
[56.] Yutaka W, Shinsuke S, Ozaki S, Masato H (1996) Synthesis of phosphorofluoridate analogs of myo-inositol 1,4,5-tris(phosphate) and their biological activity. Chem Commun 15: 1815-1816.
[57.] Ozaki S, Yutaka W, Tomio O, Masato H, Takashi K (1992) Synthesis and biological properties of 2-substituted myo-inositol 1,4,5-trisphosphate analogs directed toward affinity chromatography and photoaffinity labeling. Carbohydr Res 234: 189-206.
[58.] Hirata M, Watanabe Y, Ishimatsu T, Ikebe T, Kimura Y, et al. (1989) Synthetic inositol trisphosphate analogs and their effects on phosphatase, kinase, and the release of calcium. J BiolChem 264: 20303-20308.
[59.] Hirata M, Watanabe Y, Ishimatsu T, Yanaga F, Koga T, et al. (1990) Inositol 1,4,5-trisphosphate affinity chromatography. BiochemBiophys Res Commun 168: 379-86.
[60.] Hirata M, Watanabe Y, Kanematsu T, Ozaki S, Koga T (1995) D-myo-Inositol 1,4,5-triphosphate analogs substituted at the 3-hydroxyl group. Biochimica et BiophysicaActa, General Subjects 1244: 404-410.
[61.] Baron CB1, Ozaki S, Watanabe Y, Hirata M, LaBelle EF, et al. (1995) Inositol 1,4,5-trisphosphate binding to porcine tracheal smooth muscle aldolase. J Biol Chem 270: 20459-20465.
[62.] Watanabe Y, Motohiro M, Takao M, Ozaki S (1989) Highly efficient protection by the tetraisopropyldisiloxane-1,3-diyl group in the synthesis of myo-inositol phosphates as inositol 1,3,4,6-tetrakisphosphate. J. Chem Soc Chem Commun 8: 482-483.
[63.] Ozaki S, Yoshihisa K, Hiroyuki N, Shinji Y, Yutaka W (1987) Synthesis of D-myo-inositol 1,3,4,5-tetrakisphosphate. Tetrahedron Letters 28: 4691-4694.
[64.] Watanabe Y, Tomoiti S, Takahiro F, Ozaki S (1990) A short step and practical synthesis of myo-inositol 1,3,4,5-tetrakisphosphate. Chem Pharm Bull 38: 562-563.
[65.] Ozaki S, Lei L, Tomio O, Yutaka W, Masato H (1994) A convenient chemo-enzymic synthesis of D- and L-myo-inositol 1,4,5,6tetrakisphosphate. Carbohyd Res 259: 307-10.
[66.] Ozaki S, Xiang-Zheng K, Yutaka W, Tomio O (1998) Synthesis of unsaturated phosphatidyl inositol-3,4,5-trisphosphate. Chinese J Chem 16: 51-57.
[67.] Hashii M, Hirata M, Ozaki S, Nozawa Y, Higashida H (1994) Ca2+ influx evoked by inositol-3,4,5,6-tetrakisphosphate in ras-transformed NIH/3T3 fibroblasts. FEBS Lett 340: 276-280.
[68.] Hirata M, Kimura Y, Ishimatsu T, Yanaga F, Shuto T, et al. (1991) Synthetic inositol 1,3,4,5-tetrakisphosphate analogues. Biochemical J 276(Pt 2), 333-336.
[69.] Kimura Y, Kanematsu T, Watanabe Y, Ozaki S, Koga T (1991) Synthetic inositol 1,3,4,5-tetrakisphosphate analogs and their effect on the binding to microsomal fraction of rat cerebellum. Bio chim Bio phys Acta 1069: 218-222.
[70.] Hirata M, Narumoto N, Watanabe Y, Kanematsu T, Koga T (1994) DL-myo-inositol 1,2,4,5-tetrakisphosphate, a potent analog of D-myoinositol 1,4,5-trisphosphate. Mol Pharmacol 45: 271-276.
[71.] Ozaki S, Yasuji k, Lei L, Yutaka W, Yuichi K, et al. (1994) Synthesis of 2-substituted myo-inositol 1,3,4,5-tetrakis(phosphate) and 1,3,4,5,6-pentakis(phosphate) analogs. Bulletin of the Chemical Society of Japan 67: 1058-1063.
[72.] Takahiko A, Hiroyuki N, Takaaki K, Ozaki S (1994) Stereodivergent synthesis of optically active a-hydroxy acids via diastereoselective reduction of a-keto esters derived from L-quebrachitol. Bulletin of the Chemical Society of Japan 67: 180-188.
[73.] Yutaka W, Eiji E, Masanao J, Ozaki S (1993) Phosphonium salt methodology for the synthesis of phosphoric monoesters and diesters and its application to selective phosphorylation. Tetrahedron Letters 34: 497-500.
[74.] Watanabe Y, Hirofuji Y, Ozaki S (1994) Synthesis of a phosphatidylinositol 3,4,5-trisphosphate. Tetrahedron Letters 35: 123-124.
[75.] Yutaka W, Masaya T, Ozaki S (1995) Synthesis of 1D-distearoylphosphatidyl-myo-inositol 3,4,5-tris(dihydrogen phosphate). Tetrahedron 51: 8969-8976.
[76.] Ozaki S, Xiang ZK, Yutaka W, Tomio O (1998) Synthesis of unsaturated phosphatidyl inositol-3,4,5-trisphosphate. Chinese J Chem 16: 51-57.
[77.] Yutaka W, Takashi Y, Ozaki S (1996) Regiospecific Synthesis of 2,6-Di-O-(a -D-mannopyranosyl)phosphatidyl-D-myo-inositol. J Org Chem 61: 14-15.
[78.] Yutaka W, Masato H, Tomio O, Toshitaka K, Ozaki S (1991) Synthesis and characterization of a photoaffinity probe possessing biotinyl and azidobenzoyl moieties for [IP.sub.3]-affiniated protein. Bioorganic and Medicinal Chemistry Letters 1: 399-402.
[79.] Kanematsu T, Takeya H, Watanabe Y, Ozaki S, Yoshida M (1992) Putative inositol 1,4,5-trisphosphate binding proteins in rat brain cytosol. J Biolo Chem 267: 6518-25.
[80.] Kamata H, Hirata M, Ozaki S, Kusaka I, Kagawa Y (1992) Partial purification and reconstitution of inositol 1,4,5-trisphosphate receptor/ calcium channel of bovine liver microsomes. J Biochem 111: 546-52.
[81.] Ozaki S, Yutaka W, Masato H, Yomio O, Takashi K, et al. (1993) Inositol 1,4,5-triphosphate Affinity Chromatography. Fishing out Ins (1,4,5) P3-recognizable Protein. Drug Design for neuroscience Alan Kozikowski (Ed.) Raven Press, New York: NY, 417-434.
[82.] Takashi K, Yoshio M, Yutaka W, Ozaki S, Toshitaka K, et al. (1996) A new inositol 1,4,5-trisphosphate binding protein similar to phospholipase C-d 1. Bioche J 313: 319-325.
[83.] Yoshida M, Kanematsu T, Watanabe Y, Koga T, Ozaki S, et al. (1994) D-myo-Inositol 1,4,5-trisphosphate-binding proteins in rat brain membranes. J Biochem 115: 973-980.
[84.] Yagisawa H, Hirata M, Kanematsu T, Watanabe Y, Ozaki S, et al. (1994) Expression and characterization of an inositol 1,4,5-trisphosphate binding domain of phosphatidylinositol-specific phospholipase C-delta 1. J BiolChem 269: 20179-20188.
[85.] Hirata M, Kanematsu T, Sakuma K, Koga T, Watanabe Y, et al. (1994) D-myo-Inositol 1,4,5-trisphosphate binding domain of phospholipase C-d 1. BiochemBiophys Res Commun 205: 1563-1571.
[86.] Ozaki S, Yasuji K, Lei L, Yutaka W, Yuichi K, et al. (1994) Synthesis of 2-substituted myo-inositol 1,3,4,5-tetrakis(phosphate) and 1,3,4,5,6-pentakis(phosphate) analogs. Bulletin of the Chemical Society of Japan 67: 1058-1063.
[87.] Moriya S, Kazlauskas A, Akimoto K, Hirai S, Mizuno K, et al. (1996) Platelet-derived growth factor activates protein kinase C epsilon through redundant and independent signaling pathways involving phospholipase C gamma or phosphatidylinositol 3-kinase. ProcNatlAcadSci U S A 93: 151-155.
[88.] Hogan SP, Foster PS, Hansbro PM, Ozaki S, Denborough MA (1994) Detection and partial purification of inositol 1,4,5-trisphosphate 3-kinase from porcine skeletal muscle. Cell Signal 6: 233-243.
[89.] Foster PS, Hogan SP, Hansbro PM, O'Brien R, Potter BV, et al. (1994) The metabolism of D-myo-inositol 1,4,5-trisphosphate and D-myo-inositol 1,3,4,5-tetrakisphosphate by porcine skeletal muscle. Eur J Biochem 222: 955-964.
[90.] Matsuzaki H, Konishi H, Tanaka M, Ono Y, Takenawa T, et al. (1996) Isolation of the active form of RAC-protein kinase (PKB/Akt) from transfected COS-7 cells treated with heat shock stress and effects of phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 4,5-bisphosphate on its enzyme activity. FEBS Letters 396: 305-308.
[91.] Yagisawa H, Hirata M, Kanematsu T, Watanabe Y, Ozaki S, et al. (1994) Expression and characterization of an inositol 1,4,5-trisphosphate binding domain of phosphatidylinositol-specific phospholipase C-d 1. J BiolChem 269: 20179-20188.
[92.] Uwe B, Michael H, Marcus H, Christina D, Werner F, et al. (1999) A novel A-isoform-like inositol 1,4,5-trisphosphate 3-kinase from chicken erythrocytes exhibits alternative splicing and conservation of intron positions between vertebrates and invertebrates. Gene 228: 61-71.
[93.] Ozak S, Ike Y, Mizuno H, Ishikawa K, Mori H (1977) Synthesis of 1-carbamoyl-5-fluoouacils. Bull Chem Soc Jpn 50: 2406-2412.
[94.] Ozaki S (1996) Synthesis and antitumor activity of 5-fluorouracil derivatives. Med Res Rev 16: 51-86.
[95.] Polymyxin B Sulfate, Merck Index 12 (Edn). 301.
[96.] Ozakiv S (1977) Orally active cytostatic deriv of 5-fluorouracil USP 4071519.
[97.] Ozaki S (1972) Recent advances in isocyanate chemistry Chem Review 72: 455-497.
[98.] Fux M, Levine J, Aviv A, Belmaker RH (1996) Inositol treatment of obsessive-compulsive disorder. Am J Psychiatry 153: 1219-1221.
[99.] Palatnik A, Frolov K, Fux M, Benjamin J (2001) Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder". J Clin Psycho pharmacol 21: 335-339.
[100.] Levine J, Barak Y, Gonzalves M, Szor H, Elizur A, et al. (1995) Double-blind, controlled trial of inositol treatment of depression. Am J Psychiatry 152: 792-794.
[101.] Taylor MJ, Wilder H, Bhagwagar Z, Geddes J (2004) Inositol for depressive disorders. Cochrane Database Syst Rev: CD004049.
[102.] Harris BA, Robishaw JD, Mumby SM, Gilman AG (1985) Molecular cloning of complementary DNA for the alpha subunit of the G protein that stimulates adenylatecyclase. Science 229: 1274-1277.
[103.] Seeds NW, Gilman AG (1971) Norepinephrine stinulated increase of cyclic AMP levels in developing mouse brain cell cultures. Science 174: 292.
[104.] Gilman AG, Nirenberg M (1971) Regulation of adenosine 3',5'-cyclic monophosphate metabolism in cultured neuroblastoma cells. Nature 234: 356-358.
[105.] Brian K (2004) The state of GPCR research in 2004: Nature Reviews Drug Discovery. Nat Rev Drug Discov 3: 577-626.
[106.] Duke Medicine News and Communications (2008-09-28) Duke Medicine Physician-Scientist Receives National Medal of Science. Duke Health.org. Retrieved 2013-01-14.
[107.] Robert J (2009) Biomedicine. BBVA Foundation Frontiers of Knowledge Awards. Retrieved.
[108.] Maruyama T, Kanaji T, Nakade S, Kanno T, Mikoshiba K (1997) 2APB, 2-aminoethoxydiphenyl borate, a membrane-penetrable modulator of Ins(1,4,5)[P.sub.3]-induced Ca2+ release. J Biochem 122: 498-505.
[109.] Iwasaki H, Mori Y, Hara Y, Hara Y, Uchida K, et al. (2001) 2-Aminoethoxydiphenyl borate (2-APB) inhibits capacitative calcium entry independently of the function of inositol 1,4,5-trisphosphate receptors. Receptors Channels. 7: 429-439.
[110.] Bilmen JG, Michelangeli F (2002) Inhibition of the type 1 inositol 1,4,5-trisphosphate receptor by 2-aminoethoxydiphenylborate. Cell Signal 14: 955-960.
[111.] Ma HT, Venkatachalam K, Parys JB, Gill DL (2002) Modification of store-operated channel coupling and inositol trisphosphate receptor function by 2-aminoethoxydiphenyl borate in DT40 lymphocytes. J. Biol. Chem 277: 6915-6922.
[112.] Dobrydneva Y, Blackmore P (2001) 2-Aminoethoxydiphenyl borate directly inhibits store-operated calcium entry channels in human platelets. Mol Pharmacol 60: 541-552.
[113.] Bilmen JG, Wootton LL, Godfrey RE, Smart OS, Michelangeli F (2002) Inhibition of SERCA Ca2+ pumps by 2-aminoethoxydiphenyl borate (2APB). 2-APB reduces both Ca2+ binding and phosphoryl transfer from ATP, by interfering with the pathway leading to the Ca2+-binding sites. Eur J Biochem 269: 3678-3687.
[114.] Missiaen L, Callewaert G, De Smedt H, Parys JB (2001) 2-Aminoethoxydiphenyl borate affects the inositol 1,4,5-trisphosphate receptor, the intracellular Ca2+ pump and the non-specific Ca2+ leak from the non-mitochondrial Ca2+ stores in permeabilized A7r5 cells. Cell Calcium 29: 111-116.
[115.] Peppiatt CM, Collins T, Mackenzie L, Conway SJ, Holmes AB, et al. (2003), 2-Aminoethoxydiphenyl borate (2-APB) antagonises inositol 1,4,5-trisphosphate-induced calcium release, inhibits calcium pumps and has a use-dependent and slowly reversible action on store-operated calcium entry channels. Cell Calcium 34: 97-108.
[116.] Luo D, Broad LM, Bird GS, Putney JW Jr (2001) Signaling pathways underlying muscarinic receptor-induced [Ca2+]i oscillations in HEK293 cells. J BiolChem 276: 5613-5621.
[117.] Bootman MD, Young KW, Young JM, Moreton RB, Berridge MJ (1996) Extracellular calcium concentration controls the frequency of intracellular calcium spiking independently of inositol 1,4,5-trisphosphate production in HeLa cells. Biochem. J 314: 347-354.
[118.] Mackenzie I, Bootman MD, Berridge MJ, Lipp PJ (2001) Predetermined recruitment of calcium release sites underlies excitation-contraction coupling in rat atrial myocytes. J. Physiol 530: 417-429.
[119.] Lipp P, Laine M, Tovey SC, Burrell KM, Berridge MJ, et al. (2000) Functional InsP3 receptors that may modulate excitation-contraction coupling in the heart. CurrBiol 10: 939-942.
[120.] Mackenzie L, Bootman MD, Laine M, Berridge MJ, Thuring J, et al. (2002) The role of inositol 1,4,5-trisphosphate receptors in Ca(2+) signalling and the generation of arrhythmias in rat atrial myocytes. J Physiol 541: 395-409.
[121.] Proven A, Roderick HL, Conway SJ, Berridge MJ, Horton JK, et al. (2006) Inositol 1,4,5-trisphosphate supports the arrhythmogenic action of endothelin-1 on ventricular cardiac myocytes. J Cell Sci 119: 3363-3375.
[122.] Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4: 517-529.
[123.] Berridge MJ (2006) Remodelling Ca2+ signalling systems and cardiac hypertrophy. Biochem Soc Trans 34: 228-231.
[124.] Berridge MJ (2006) Calcium microdomains: organization and function. Cell Calcium 40: 405-412.
[125.] Zhou H, Iwasaki H, Nakamura T, Nakamura K, Maruyama T, et al. (2007) 2-Aminoethyl diphenylborinate analogues: selective inhibition for store-operated Ca2+ entry. Biochem Biophys Res Commun 352: 277-282.
[126.] Suzuki AZ, Ozaki S, Goto J, Mikoshiba K (2010) Synthesis of bisboron compounds and their strong inhibitory activity on store-operated calcium entry. Bioorg Med Chem Lett 20: 1395-1398.
[127.] Goto J, Suzuki AZ, Ozaki S, Matsumoto N, Nakamura T, et al. (2010) Two novel 2-aminoethyl diphenylborinate (2-APB) analogues differentially activate and inhibit store-operated Ca(2+) entry via STIM proteins. Cell Calcium 47: 1-10.
[128.] Mikoshiba K, Ozaki S, Suzuki A, Nakamura T (2007) Preparation of bisboron compounds controlling calcium concentration in cells. PCT Int Appl.
[129.] Mikoshiba K, Ozaki S, Ebisui E (2009) KokaiTokkyoKoho, Japan.
[130.] Mikoshiba K, Nukina N, Ozaki S (2011) US 2011/0212919 A1, PCT Int Appl.
[131.] Ozaki S, Suzuki AZ, Bauer PO, Ebisui E, Mikoshiba K (2013) 2-Aminoethyl diphenylborinate (2-APB) analogues: regulation of Ca2+ signaling. BiochemBiophys Res Commun 441: 286-290.
[132.] Ozaki S (2014) 2-Aminoethyldiphenylborinate (2APB) analogues. Part 2. Regulators of Ca2+ release and consequent cellular processes. Archives Physiol 1: 1-6.
[133.] Ozaki S (2014) 2-Aminoethyldiphenylborinate (2APB) analogues. Part 4 Poly-boron compounds: Regulators of Ca2+ release and consequent cellular processes. J Bioengineer and Biomedical Sci 4:134.
[134.] Blackshear PJ, Holloway PA, Alberti KG (1975) Factors regulating amino acid release from extrasplanchnic tissues in the rat. Interactions of alanine and glutamine. Biochem J 150: 379-387.
[135.] Ozaki S (2014) Signal transduction and discovery of regulator of Ca release and cellular process. J Med Res Prac 3: 20-24.
[136.] 911 is available from Tokyo Chemical Industry Co.Ltd.
[137.] Berridge MJ (1098) Neural calcium signaling. Neuron 2: 13-26.
[138.] Berridge MJ (2010) Calcium hypothesis of Alzheimer's disease. Pflugers Arch 459: 441-449.
[139.] Berridge MJ (2013) Dysregulation of neural calcium signaling in Alzheimer disease, bipolar disorder and schizophrenia. Prion 7: 2-13.
[140.] Berridge MJ (2011) Calcium signalling and Alzheimer's disease. Neurochem Res 36: 1149-1156.
[141.] Berridge MJ (2013) Dysregulation of neural calcium signaling in Alzheimer disease, bipolar disorder and schizophrenia. Prion 7: 2-13.
[142.] Bauer PO, Hudec R, Ozaki S, Okuno M, Ebisui E, et al. (2011) Genetic ablation and chemical inhibition of IP3R1 reduce mutant huntingtin aggregation. Biochem Biophys Res Commun 416: 13-17.
[143.] Bauer PO, Hudec R, Goswami A, Kurosawa M, Matsumoto G, et al. (2012) ROCK-phosphorylated vimentin modifies mutant huntingtin aggregation via sequestration of IRBIT. Mol Neurodegener 7: 43.
[144.] Ozaki S (2014) 2-Aminoethyl Diphenylborinate (2-APB) Analogues: Part 3-Regulators of Huntington Aggregation and Transglutaminase. J Bioengineering and Biomedical Sci 4: 1-7.
Shoichiro Ozaki *
The Institute of Physical and Chemical Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
* Corresponding author: Ozaki S, The Institute of Physical and Chemical Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan, Tel: +81 0467670991; E-mail:firstname.lastname@example.org
Received date: December 19, 2014, Accepted date: January 19, 2015, Published date: January 26, 2015
|Printer friendly Cite/link Email Feedback|
|Publication:||Biology and Medicine|
|Date:||Apr 1, 2015|
|Previous Article:||Microbial landscape of surgical hospital.|
|Next Article:||The efficiency of garlic extract in prevention of lead acetate toxicity on fallopian tube--a hormonal study.|