Разработка научно-методических основ и биотестсистем для скрининга иммуносупрессоров
Диссертация
Среди вторичных микробных метаболитов, получивших важное практическое значение не за счет своей антибиотической активности, первое место несомненно занимает и м муносу прессор циклоспорин А. Этот циклический ундекапептид — представитель семейства циклоспоринов в настоящее время, производимый фирмой «Sandoz», широко используется при пересадке органов и тканей, а также при лечении аутоиммунных… Читать ещё >
Содержание
- I. ВВЕДЕНИЕ
- II. ОБЗОР ЛИТЕРАТУРЫ
- Глава 1. Вторичные метаболиты микроорганизмов. Новые аспекты их использования и проблемы скрининга
- 1. 1. К истории открытия циклоспорина А
- 1. 2. Продуценты циклоспоринов
- 1. 3. Химия циклоспорина А
- 1. 4. Биосинтез циклоспорина А. Циклоспорин син-тетаза
- 1. 5. Направленный биосинтез циклоспорина А
- 1. 6. Эффекты циклоспорина, А на уровне клеток и межклеточных взаимодействий
- 1. 7. Новые иммуносупрессоры природного происхождения
- 1. 8. Внутриклеточные мишени циклоспорина A, FK и рапамицина
- 1. 9. Некоторые проблемы моделирования при поиске природных иммуносупрессоров
- 1. 10. Биологическая активность циклоспориновых структур, не связанная с иммуносупрессорным эффектом
- III. ЭКСПЕРИМЕНТАЛЬНАЯ ЧАСТ
- Глава 1. Материалы и методы
- 1. 1. Антибиотики и реагенты
- 1. 2. Тест-объекты (виды и штаммы грибов)
- 1. 3. Питательные среды
- 1. 4. Определение антифунгальной активности циклоспорина, А одного и в комбинации с другими биологически активными веществами
- 1. 5. Изучение морфологических особенностей мицелия в присутствии циклоспорина А
- 1. 6. Ультраструктурный анализ действия циклоспорина, А на клетки грибов
- 1. 7. Получение липосомальных препаратов антибиотиков
- 1. 8. Получение протопластов из клеток Tolypocladium inflatum subsp. blastosporum
- 1. 9. Определение нарушения проницаемости цито-плазматической мембраны
- 1. 10. Определение белка и нуклеиновых кислот в клетках грибов
- 1. 11. Определение активности протеолитических ферментов
- 1. 12. Математическая обработка результатов
- Глава 2. Особенности действия циклоспорина, А на грибы
- 2. 1. Антифунгальная активность циклоспорина, А и его влияние на морфологические свойства при росте Aspergillus niger J 37 а в различных условиях культивировании
- 2. 2. Морфологические особенности культуры Aspergillus niger 137 а при росте на агаризованных средах содержащих циклоспорин А
- 2. 3. Морфология клеток Aspergillus niger 137а, растущих в присутствии циклоспорина, А в условиях глубинного культивирования
- 2. 4. Влияние циклоспорина, А на морфологические свойства Penicillium lucidum штамм 41 В
- 2. 5. Морфологические аномалии Aspergillus niger и Tolypocladium inflatum, вызываемые новыми природными иммуносупрессорами
- Глава 3. Влияние некоторых биологически активных соединений на антифунгальную активность циклоспорина А
- 3. 1. Влияние макролидных структур на антифунгальный эффект циклоспорина А
- 3. 2. Влияние некоторых новых иммуносупрессоров на антифунгальный эффект циклоспорина А
- 3. 3. Влияние на активность циклоспорина, А фузидина и аминогликозидных антибиотиков
- 3. 4. Влияние на активность циклоспорина, А соедине ний, включенных в биоэнергетический метаболизм
- Глава 4. Изучение действия циклоспорина, А на клетки
- Aspergillus niger методом электронной микроскопии
- Глава 5. Действие циклоспорина, А на барьерные функции цитоплазматической мембраны Aspergillus niger 137 а
- 5. 1. Действие циклоспорина на синтез бежа и нуклеиновых кислот
- 5. 2. Действие липосомального препарата циклоспорина, А на барьерные функции цитоплазма-тической мембраны Aspergillus niger 137а
- 5. 3. Совместное действие циклоспорина, А и амфоте рицина В в свободной и липосомальной форме на проницаемость цитоплазматической мембраны Aspergillus niger 137а
- 5. 4. Действие циклоспорина, А и амфотерицина В на проницаемость мембраны протопластов Tolypocla-dium inflatum
- Глава 6. Влияние циклоспорина, А на протеолитическую активность Aspergillus niger 137a (in vitro и in vivo)
- IV. ОБСУЖДЕНИЕ РЕЗУЛЬТАТОВ
- V. ВЫВОДЫ
Список литературы
- Андреев А.Ю., Михайлова Л. М., Старков A.A. Закрытие Ca -зависимой поры циклоспорином А: роль ионов магния, адениновых нуклеотидов и конформационного состояния АДФ/АТФ антипортера. Биохимия 1994- 59: 10: 1589−1597.
- Аравийский P.A., Потыльчанская О. Л. Чувствительность диморфных клеток Candida albicans к полиеновым антибиотикам и их сочетаниям с другими биологически активными веществами. Антибиотики и медицинская биотехнология 1987- 5: 354 357.
- Березовская Л.Н., Грязнова Н. С., Байрамишвили Д. И., Яроц-кий C.B. Проблемы создания липосомальных лекарственных форм антибиотиков. Антибиотики и химиотерапия 1990- 35: 10: 31−35.
- Бибикова М.В., Рыбакова A.M., Иваницкая Л. П. и др. Система скрининга природных иммуносупрессоров. Антибиотики и химиотерапия 1991- 36: 3: 17−20.
- Бибикова М.В., Рыбакова A.M., Спиридонова И. А. и др. Влияние стимуляторов Н-АТФазы на биосинтез циклоспорина. Антибиотики и химиотерапия 1994- 39: 4: 8−11.
- Бибикова М.В., Иваницкая Л. П. Поиск ингибиторов ферментов природного происхождения. Антибиотики и химиотерапия 1991- 1.
- Бибикова М.В., Рыбакова А. М., Востров С. Н., Иваницкая Л. П. и др. Поиск продуцентов ингибиторов синтеза холестерина. Первый Советско-Американский симпозиум по антибиотикам и химиотерапии. Тез. Докладов, Москва 1988- с. 15.
- Е^лай В.И., Эллинская И. А. Экспериментальный морфогенез грибов. Микология и фитопаталогия 1972- 8: 3: 193−200.8 а. Билай В. И. Методы экспериментальной микологии. Киев: Изд. «Наукова думка» 1982.
- Булгакова В.Г., Новожилова Т. Ю., Орлова Т. И., Полин А. Н. Изменение грамицидином S и его производными проницаемости цитоплазматических мембран стрептомицетов. Антибиотики и медицинская биотехнология 1986- 6: 411−416.
- Вядро М.М., Фомина И. П., Иваницкая Л. П. и др. Эффект циклоспорина на ксенотрансплантацию опухолей под капсулу почки у мышей. Антибиотики и химиотерапия 1989- 34: 4: 280−282.
- Гаузе Г. Ф., Максимова Т. С., Терехова Л. П. Изыскание продуцентов антибиотиков иммунодепрессантов группы циклоспорина среди культур грибов. Микология и фитопаталогия 1990: 24: 1:35−38.
- Егоров Н.С. Основы учения об антибиотиках. М. Изд. «Высшая школа» 1986- 51−55.12 а. Евлахова A.A. Энтомопатогенные несовершенные грибы. Жизнь растений 1976- 2: 439.
- Иваницкая Л.П., Бибикова М. В. и др. Штамм Tolypocladium inflatum. subsp. blastosporum продуцент циклоспорина А. Патент РФ, № 1 830 947, 27.10.88 г.
- Иваницкая Л.П., Вядро М. М. Модификаторы биологических реакций препараты с иммуномодулирующей и противоопухолевой активностью. Антибиотики и химиотерапия 1989- 34: 7: 530−534.
- Иваницкая Л.П., Хурнова Л. А., Никитин A.B. и др. Низкомолекулярные иммуномодуляторы природного происхождения. Антибиотики и медицинская биотехнология 1987- 11: 814−816.
- Иванов Ю. И. Погорелюк О.Н. Обработка результатов медико-биологических исследований на микроколькуляторах. М. Медицина 1990
- Калакуцкий JI.B. Агре Н. С. Развитие актиномицетов. М. Наука 1977- 286.
- Кушнарева Ю.Е., Михайлова JIM., Андреев А. Ю. Низкие концентрации циклоспорина, А закрывают Са2±зависимую пору внутренней мембраны митохондрий в отсутствие дополнительных эффекторов. Биохимия 1995: 60: 9: 1502−1511.
- Никитин A.B. Иммунофармакология циклоспорина А. Антибиотики и химиотерапия, 1986- 31: 1: 56−66.
- Сазыкин Ю.О. Антибиотики как биохимические реагенты. М. ВИНИТИ, Биологическая химия 1984- 20: 3−15.
- Сазыкин Ю.О., Г.Н. Телеснина, П. Л. Иваницкая Л.П. и др. Влияние циклоспорина на некоторые метаболические процессыi, А Л. Л.грибов. Антибиотики и химиотерапия 1994- 39: 7: 3−9.
- Сазыкин Ю.О., Навашин Н. С. Антибиотики и оболочка микробной клетки. М ВИНИТИ, Биотехнология 1991- 31: 1−10.
- Спирин A.C. Спектрофотометрическое определение суммарного количества нуклеиновых кислот. Биохимия 1958- 23: В: 5: 656−662.
- Телеснина Г. Н., Крестьянова И. Н., Сазыкин Ю. О. и др. Получение протопластов Xanthomonas rubriliensis. Антибиотики и химиотерапия 1992- 7: 4: 3−8.
- Телеснина Г. Н., Сотникова И. В., Иваницкая Л. П. и др. Биоэнергетические процессы у изогенных продуцентов циклоспорина с различным уровнем биосинтеза. Тезисы 7-й Национальной конференции по производству и применению антибиотиков. Болгария, Разград, 1990.
- Урбах В.Ю. Статический анализ в биологических и медицинских исследованиях. М.: Изд. «Медицина «1975.
- Феофилова Е.П. Вторичный метаболизм и дифференциация микроскопических грибов. Успехи микробиологии 1981- 4: 78−86.27 а. Феофилова Е. П. Клеточная стенка грибов. М. Изд. «Наука» 1983.
- Хурнова Л.М., Иваницкая Л. П. Низкомолекулярные иммуномодуляторы природного происхождения. Антибиотики и химиотерапия 1989- 34: 10: 786−792.
- Шальнев Б.И., Бибикова М. В., Иваницкая Л. П. и др. Иммуносупоессивные свойства отечественного псепаоата ник1 X ллоспоринового ряда. Гематология и трансфузия 1988- 10: 116 120.
- Aminzadeh A. Effect of cyclosporin A on the order and dynamics DPPC model membrane systems. Iran J. Chem. Chem. Eng. 1993- 12:2: 49−53 (CA 1995- 122: 11: 126 779).
- Andreeva L., Tanver A., Crompton M., Evidence for the involvement of a membrane-associated cyclosporin A -binding protein in the Ca2±activated inner membrane pore of heart mitochondria. Eur. J. Biochem. 1995- 230: 3: 1125−1132.
- Aotani Y., Nagata H., Yoshida M. Lymphostin (LK6-A), a novel immunosuppressant from Streptomyces sp. KYI 1783. Structural elucidation. J. Antibiotics 1997- 50: 543−545.
- Aparico J.F., Molnar I., Schwecke T. et al. Organization of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: analysis of the enzymatic domains in the modular polyketide synthase. Gene 1996- 169: 9−16.
- Arx J.A. Tolypocladium, a synonym of Beauveria. Mycotaxon 1986- 25: 1: 153−158.
- Barisic К. Cyclophilin, a cellular target for cyclosporin A. Acta Pharm. 1995- 45: 3: 413−420.
- Bartz A., Steven R., Hohenwalter E. et al. Inhibition of human immunodeficiency virus replication by nonimmunosuppessive analogs of cyclosporin A. Proc. Nat. Acad. Sci. USA 1995- 92: 12: 5381−5385.
- Beketic-Oreskovic L., Duran G.E. Decreased mutation rate for cellular resistance to doxorubicin and suppression of mdrl gene activation by the cyclosporin PSC833. J. Natl. Cancer Inst. 1995- 87: 21: 1593−1602.
- Bell A., Roberts H., Chappell L.H. The antiparasite effects of cyclosporin A: possible drug targets and clinical application. Gen. Pharmacol. 1996- 27: 6: 963−971.
- Bell A., Wernli В., Franklin R.M. Roles of peptidyl-prolyl cis-trans isomerase and calcineurin in the mechanisms of antimalarial action of cyclosporin A, FK506, and rapamycin. Biochem. Pharmacol. 1994- 48: 3: 495−503.
- Beppu Т., Morphological abnormalities of eucaryotic cells induced by microbial metabolites as indices to direct nobel physiological activities. Protein, Nucleic Acid and Enzymes 1993- 38: 1639−1646.
- Berdy J. Are Actinomycetes exhausted as a source of secondary metabolites. Биотехнология 1995- 7−8: 13−34.
- Bernard P. The permeability transition pore. History and perspectives of a cyclosporin A sensitive mitochondrial channel. Progr. Cell Res. 1995- 5: 119−123.
- Bibikova M., Rybakova A., Ivanitskaya L. et al. Directed screening of immunosuppressors such as cyclosporin A. Abstr. of II Intern. Symposium «New bioactive metabolites from microorganisms» 1988- 87.
- Bierer B.E., Mattila P. S., Standaert R.F. et al. Two distinctsignal transmission pathways in T lymphocytes are inhibited by complex formated between an immunophilin and either FK506 or rapamycin. Proc. Nat. Acad. Sci. USA 1990- 87: 23: 9231−9235.
- Bladen C., Vincent S.R. Characterization and localization of 3H.-cyclosporine A binding sites in rat brain. NeuroReport 1994- 5:11: 1386−1388.
- Borel J.F. Comparative study of in vitro and in vivo drug effects on cell-mediated cytotoxicity. Immunology 1976- 31: 631−637.
- Borel J.F. Feurer C., Magnee C. et al. Effects of the new antilymphocytic peptide cyclosporin A in animals. Immunology 1977- 2: 6: 1017−1028.
- Borel J.F. Pharmacology of cyclosporin (Sandimmune) IV. Pharmacological properties in vivo. Pharmacol Rev. 1989- 41: 3: 259 371.
- Borel J.F., Feurer C, Gubler H.U. et al. Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions 1976- 6: 4: 468−475.
- Braijtburg J., Kobayashi D., Medoff G. et al. Antifungal action of amphothericin B in combinations with other polyene or imidazole antibiotics. J. Infect. Dis. 1982- 146: 138−146.
- Bunjes D., Hardt C. Roelling haf M. et al. Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin-1 and interleukin-2. Eur. J. Immunol. 1981- 11: 657−666.
- Byrne K.M., Shafiee A., Nielsen J B. et al. The biosynthesis and enzymology of an immunosuppressant immunomycin produced by Streptomyces hygroscopicus var. Ascomyceticus. Develop. Ind. Microbiol. 1993- 2: 29−44.
- Calne R.Y., White D.J.G., Thiru S. et al. Cyclosporin A in patients receiving renal allografts from cadaver donors. Lancet i i 1978- 1323−1326.
- Chen T.S., Petuch B., White R. et al. Microbial transformation of immunosuppressive compounds. IV. Hydroxylation and hemiketal formation of ascomycin (immunomycin) by Streptomyces sp. MA 6970. J. Antibiotics 1994- 47: 1557−1559.
- Chopra I., Hodgson J., Metealf B. et al. The search for antimicrobial agents effective against bacteria resistant to multiple antibiotics. Antimicrob. Ag. Chemotherapy 1997- 41: 3: 497−503.
- Colombani P.M., Robb A., Hess A.D. Cyclosporin A binding to calmodulin: a possible site of action on T lymphocytes. Science 1985- 228: 337−339.
- Crompton M., Andreeva L., Tanver A. et al. On native of the cyclosporin A binding comoonent of the mitochondrial Ca2+ deoendent1. A W X Xpore. Progr. Cell Res. 1995- 5: 125−128.
- Dancer R.J., Jones A., Fairlie D. Binding of the immunosuppressant peptide cyclosporin A to calcium, zinc and cooper. Is cyclosporin A an ionofore? Aust. J. Chem. 1995- 48: 11: 1835−1841.
- Demeule M. Studies on molecular interactions betweencyclosporin A and renal membranes. Diss Abstr. Int B. 1995- 55: 7: 2575 (CA 1995- 122: 19: 230 163).
- Denesyuk A.I., Londwell J., Zavyalov V.P. et al. Cyclophilin A and an antibody against cyclosporin A resemble each other in their binding sites. Immunol. Lett. 1994: 41: 2−3: 213−216.
- Domoiseaux J.G.M.C., Beijleveld L.J., Schurerman H.T. et al. Effect in vivo rapamycin treatment on de hovo T cells development in relation to induction of autoimmune-like immunoDatholoev in the rat.1. A.
- Transplantation 1996- 62: 7: 994−1001.
- Donald V.C., Chapman F. A., Jaffee B.D. et al. The effect of new immunosuppressive drug, brequinar sodium on heart, liver, and kidney allograft rejection in the rat. Transplantation 1992- 53: 303−308.
- Dreyfuss M., Haerry E., Hoffman H. et al. Cyclosporin A and C. New metabolites from Trichoderma polysporum. Eur. J. Appl. Microbiol. 1976- 3: 2: 125−133.
- Dumont F.J., Staruch M.J., Koprak S.I. et al. Distinct mechanism of suppression of murine T cells activation by the related macrolide FK506 and rapamycin. J. Immunology 1990- 144: 251−258.
- Eberle M.K. Hiestand P. Jutzi-Eme A.M. et al. Preparation1. JLand in vitro activities of ethers of D-serine. 8 cyclosporin. J. Med. Chem. 1995- 38: 11: 1853−1864.
- Epand R.M., Epand R.F., Harkey D.L. et al. Insensitivity of a multidrug-resistant cell-line to cyclosporin. Cancer J. 1994- 7: 2: 85−90.
- Erlanser B.F. Mechanism of action of cvclosnorin. Reolv to1. W A J. «/comments. Immunol. Today 1994- 15: 5: 248.
- Fang J., Jang X., Ren L. et al. The effect of amino acids on biosynthesis of cyclosporin A. Kangshengsu 1990 15: 2: 140−141.
- Fang J., Shi J., Ju B. Isolation and structural assignment of cyclosporin B and C produced be Fusarium solani sp. № 4−11.
- Kangshengsu 1989- 14: 3: 197−201.
- Fehr T., Quesninaux V.F.J., Sangler J.-J. et al. Cymbimicin A and B, two novel eyclophilin-binding structures isolated from actinomycetes. J. Antibiotics 1997- 50: 11: 893−899.
- Fehr T., Sangier J.J., Schuler W. et al. Antascomicins A, B, C, D and E. Novel FKBP12 binding compounds from a Micromonospora strain. J. Antibiotics 1996- 49: 3: 230−233.
- Fehr T., Sanglier J.-J., Schuler W. Macrolides as antagonists of macrophilin binding immunosuppressants. WO 9, 506, 649 September 1- 1993.
- Ferreiro P.A. Pak W. Retina-soecificallv expressed novel sub1. X m> Xtypes of bovine cyclophilin. J. Biol. Chem.1995- 270: 39: 23 179−23 188.
- Fischer G. Wittmann-Liebold B. Lians K. et al. Cvcloohilinj y t^j j xand peptidyl-prolyl cis-trans isomerase are probable identical proteins. Nature 1989- 337: 6206: 476−478.
- Ford J.M., Hait W.N. Pharmacology of drugs that after multidrug resistance in cancer. Pharmacol. Rev. 1990- 42: 3: 155−199.
- Fujita T., Hamamichi N., Kiuchi M. et al. Determination of absolute configuration and biological activity of new immunosuppressants mycesteriocins D, E, F and G. J. Antibiotics 1996- 49: 9: 846−853.
- Fujita T., Inoue K., Yamamoto S. et al. Fungal metabolites. Part II. A potent immunosuppressive activity found in Isaria sinclairii metabolites. J. Antibiotics 1994- 47: 208−215.
- Gallo P., Saviano M., Rossi F. et al. Specific interaction between cyclophilin and cyclic peptides. Pept. 1994- Proc. Eur. Pept. Svmt>. 1995: 654−655.1. V X '
- Gams W. A revision of the genus Trichoderma. My col. Papers 1969- 116: 12−27.
- Gams W. Tolypocladium eine Hyphomycetengattung mit geschwollenen Phialiden. Personia 1971- 6: 185.
- Gehrt A., Erkel G., Anke Т. et al. Cycloepoxydon. 1-hydroxy-2-hydroxy-methyl-3-pent-l-enylbenzene and l-hydroxy-2-hydroxy-methyl-3-pent-l, 3,-dienylbenzene, new inhibitors of eucaryotic signal transduction. J. Antibiotics 1998- 51:5: 455−463.
- Grape U., Ihn W., Dornberger К. et al. Approaches to sceening for new bioactive microbial peptide. Биотехнология 1995- 7−8: 209 214.
- Gunji S., Arima K., Beppu T. Screening of antifungal antibiotics according to activities inducing morphological abnormalities. Agric Biol. Chem. 1983- 47: 2061−2069.
- Hait W.N., Stein J.M., Koletsky A.J. et al. Activity of cyclosporin A and a non-immunosuppressive cyclosporin on multidrug resistant leukemic cell lines. Cancer Commun. 1989- 1: 35−43.
- Hait W.N., Stein L.M., Koletsky A.J. et al. Modulation of doxorubicin (DOX) resistance by cyclosporin A (CsA) and a non-immunosuppressive homolog. Proe. Am. Acad. Cancer Res. 1987- 28: 298.
- Handschumacher R.E., Harding M.W., Rice J. et al. Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science 1984- 226: 544−546.
- Harding M.W., Handschumacher R.E., Speicher D.W. Isolation and aminoacid sequence of cyclophilin. J.Biol. Chemistry 1985−261:8547−8556.
- Hayashi M., Kim Y.-P., Takamatsu S. et al. Chlovalicin, a new cytocidal antibiotic produced by Sporothrix sp. FO-4649. I. Taxonomy, fermentation and biological activities. J. Antibiotics 1996- 49: 7: 631−634.
- Hazen K.C., Hazen B.W., Allietta M.M. Cell wall anchoring to cytoplasmic membrane of Candida albicans. FEMS Tett. 1995- 125: 23: 143−148.
- Hirtzlin J., Faerber P.M., Franklin R.M. et al. Molecular and biochemical characterization of a Plasmodium falciparum cyclosporin containing a cleavable signal sequence. Eur. J. Biochem. 1995- 232: 3: 765−772.
- Hornich E., Thurring K., Borner H. Variation of aminoaeid within the cyclosporin-cyclophilin binding domain. Synthesis of a 21-membered cyclopeptolide. Sci. Pharm. 1996- 64: 314: 463−470.
- Husi H. Zurini M.G.M. Comparative binding studies of cyclophilins to cyclosporin A and derivatives by fluorescence measurements. A nal. Biochem. 1994- 222: 1: 251−255.
- Isaas C.E., Jones A. Pickard M.A. Production of cyclosporins by Tolypocladium niveum strains. Antimicrobial. Ag. Chemotherapy 1990- 34: 1: 121−127.
- Isono K., Kobinata K., Suzuki S. Isolation and characterization of polyoxins J, K and L. New components of polyoxin complex. Agric. Biol. Chem. 1968- 32: 792−793.
- Jamamoto K., Kadobayshi M., Ueda Y. et al. Human erythrocyte cyclosporin A binding protein: purification and characterization. Pept. Chem. 1994- 32: 149−152.
- Jegorov A., Matha V., Sedmera P. Cyclosporins from Tolypocladium terricola. Phytochemistry 1995- 38: 2:403−407.
- Jette L., Potier M., Beliveau R. P-Glycoprotein is a dimer in the kidney and brain capillary membranes: effect of cyclosporin A and SDZ-PSC 833. Biochemistry 1997- 36, 45, 13 929−13 937.
- Jiang T., Acosta D.Jr. Mitochondrial Ca2+ overload in primary cultures of rat renal cortical epithelial cells by cytotoxic concentrations of cyclosporine: a digitized fluorescence imaging study. Toxicology 1995- 95: 1−3: 155−156.
- Kajira T., Furumai T., Igarashi Y. et al. Signal transduction inhibitors, hilarimicins A, B, C, D and G produced by Micromonospora. I. Taxonomy, fermentation, and physico-chemical and biological properties. J. Antibiotics 1998- 51: 4: 394−401.
- Kamigauchi T., Sakazaki R., Nagashima K. et al. Terpenins, novel immunosuppressants produced by Aspergillus Candidus. J. Antibiotics 1998- 51:4: 445−450.
- Kashani-Sabet M., Wang W., Scandon K.J. Cyclosporin A suppresses cisplatin induced c-fos gene expression in ovarian carcinoma cells. J. Biol. Chem. 1990- 265: 19: 11 285−11 288.
- Kaufmann Y., Chang A., Robb R. et all. Mechanism of action of cyclosporin A inhibition of lymphokine secretion studied with antigen-stimulated T cell hybridoma. J. Immunol. 1984- 113: 3107−3111.
- Kessler H. Loosli H.R. Oschkinat H. Assignment of the 1-H1. J J
- C and 15-N-NMR spectra of cyclosporin A in d-chloroform and de-benzene by a combination of homo and heteronuclear two dimensional techniques. Helv. Chim. Acta 1985- 68: 3: 661−681.
- Khair O.A., Devalia J.L. Abdelaziz M. et al. Effect of erythromycin on Haemophilus influenzae endotoxin-induced release of IL-6, IL-8 and slCAM-1 by cultured human bronchial epithelial cells. Eur. Respir. J. 1995- 8: 9: 1451−1457.
- Kim H.S., Han S.B., Kim H.M. et al. 41
- Demethylhomooligomyciii B, a new immunosuppressant antibiotic from Streptomyces osterogriseus. J. Antibiotics 1996- 49: 12: 1275−1277.
- Kino T., Hatanaka H., Hashimoto M. et al. FK506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation and physicochemical, and biological, and biomedical characteristics. J. Antibiotics 1987- 40: 9: 1249−1255.
- Kino T., Hatanaka H., Manata S. FK506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK506 in vitro. J. Antibiotics 1987- 40: 9: 1256−1265.
- Knott R.B., Capel M., Hansen S. et al. A small-angle X-ray scattering study of the binding of cyclosporin A to cyclophilin. J. Appl. Crystallogr. 1995- 28: 5: 546−552.
- Kobayashi H., Namikoshi M., Yoshimoto T. et al. A screening method for antimitothic and antifungal substances using conidia of Piricularia oryzae, modification and application to tropical marine fungi. J. Antibiotics 1996- 49: 9: 873−879.
- Kobel H., Traber R. Directed biosynthesis of cyclosporins. Eur. J. Appl. Microbial.Biotechnol. 1982- 4: 237−240.
- Kuhnt M., Bitsch F., Hofman H. Microbial biotransformation products of cyclosporin A. J. Antibiotics 1996- 49: 8: 781−787.
- Kurome T., Takesaka K., Kato I. Aureobasidins as a new inhibitors of P-glycoprotein in multidrug resistant tumor cells. J. Antibiotics 1998- 51:3: 353−358.
- Laatsch H., Keller M., Wolf G. et al. Oligomycin F., a new immunosuppressive homologue of oligomycin A. J. Antibiotics 1993- 4: 1334−1341.
- Lawen A Enzymic biosynthesis of cyclosporin A and analogs. Biochemie 1992- 74: 5: 511−516.
- Lawen A., Traber R., Geyl D. et al. Cell-free biosynthesis of new cyclospo-rins. J. Antibiotics 1989- 42: 8: 1283−1289.
- Lawen A., Zocher R. Cyclosporin synthetase. The most complex peptide synthesizing multienzyme polypeptide so far described. J Biol. Chem. 1990- 265: 19: 11 355−11 360.
- Lea T. P., Sands J. M. Evidence that the inhibition of Na+/K+ ATF-ase activity by FK 506 involves calcineurin. Kidney Int. 1994- 46: 3: 647−652
- Li C., Deng M. Induced variations and selection of cyclosporin-producing strains. Nanjing Daxue Xuebao 1989- 25: 3: 146 152.
- Liu J., Farmer J.D., Lane W.S. et al. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 1991−66: 807−815.
- Lowry O.H., Rosenbrough N.J., Farr A.L. et al. Protein measurement with the Falin phenol reagent. J. Biol. Chem. 1951- 193: 265−275.
- Maesaki S., Kohno S., Kaku M. et al. Effect of antifungal agent combinations administered simultaneously and sequentially against Aspergillus fumigatus. Antimicrob. Ag. Chemotherapy 1994- 38: 12: 2843−2845.
- Magae J., Matsubara H., Aotsuka N. et al. Interleukin-2 does not overcome suppression of graft rejection by cyclosporin on T cells properties in vivo. Cell Immunol. 1996- 173: 2: 276−281.
- Magae J., Miller M.W., Nagai K. et al. Effect of metacycloprodigiosin an inhibitor of killer T cells on murine skin and heart transplants. J. Antibiotics 1996- 49: 1: 86−90.
- Matouschek A., Rospert S., Schmid K. et al. Cyclophilin catalyzes protein folding in yeast mitochondria. Proc.Nat. Acad. Sei.
- USA 1995- 92: 14:6319−6321.
- Matsui H., Hatase O. Molecular recognition of caicineurin by immunosuppressant FK506 and cyclosporin A. Jikken Igaku 1995- 13: 6: 778−781 (CA 1995- 123: 1: 7).
- Michaeli M., Damcani D., Michelutti A. et al. P-170 dependent multidrug resistance. Restoring full sensitivity to idarubicin with verapamil and cyclosporin A derivatives. Haematologica 1994- 79: 2: 119−126.
- Michowitz M., Dayan-Avidan G., Bar-Shira-Maymon B. et al. Drug resistance and its counteraction by cyclosporin A in function of metastatic potential in the Lewis lung carcinoma system. Cell. Mol. Biol. (Paris) 1994- 40: 4: 551−560.
- Morikawa K., Oseka F., Morikawa S. et al. Immunomodulatory effects of three macrolides, midecamycin, josamycin, and clarithromycin on human T lymphocyte function in vitro. Antimicrob. Ag. Chemotherapy 1994- 38: 11: 2643−2647.
- Morino T., Masuda A., Yamada M. et al. Stevastelins, novel immunosuppressants produced by Penicillium. J. Antibiotics 1994- 47: 1341−1343.
- Morino T., Shimada K., Masuda A. et al. Stevastelin A3, D3 and E3, novel congeners from a high producing mutant of Penicillium sp. J. Antibiotics 1996- 49:10:1049−1059.
- Nagata H., Ochiai K., Aotani Y. et al. Lymphostin (LK6-A), a novel immunosuppressant from Streptomyces sp. KYI 1783. Taxonomyof the producing organism, fermentation, isolation and biological properties. J. Antibiotics 1997- 50: 7: 537−542.
- Nakajima H., Hamasaki T., Tanaka K. et al. Production of cyclosporin by fungi belonging to the genus Neocosmospora. Agric. Biol. Chem. 1989−53: 8: 2291−2292.
- Nakamura AS., Nagai K., Suzuki S. et al. Selective suppression by prodigiosan of the mitogenic response of murine splenocytes J. Antibiotics 1986- 39: 1155−1159.
- Nelson C., Zahn Z. Reversion of P-glycoprotein mediated multidrug resistance to vincristine and adriamycin derivative in human neuroblastoma cell lines. Int. J. Oncol. 1994- 5: 5: 1037−1042.
- Nielsen J.B., Foor F., Parent S.A. et al. Targets for the immunosuppressive drugs FK506 and cyclosporin in yeast. Dev. Ind. Microbiol. Ser. 1993- 33: 157−164.
- Nishida H., Sakakibara T., Aoki F. et al. Generation of novel rapamycin structures by microbial manipulations. J. Antibiotics 1995- 48: 657−666.
- Osieka R., Seeber S., Pannenbacker R. Enhancement of etoposide-induced cytotoxicity by cyclosporin A. Cancer Chemother. Pharmacol. 1986- 18: 3: 198−202.
- Page A.P., Kumar S., Carlow C.K.S. Parasite cyclophilins and antiparasite activity of cyclosporin A. Parasitol. Today 1995- 11: 10: 385−388.
- Pahl H.L., Kraub B., Schulze-Osthoff K. et al. Theimmunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kB. J.Exp. Med. 1996- 183: 1829−1840.
- Park J., Yaseen N., Hoyan P.G. et al. Phosphorylation of the transcription factor NFATp inhibits its DNA binding activity in cyclosporin A-treated human B and T cells. J. Biol. Chem. 1995- 270: 35: 20 653−20 659.
- Paslari L., Pinto M., Morange M. GRP78 induction by cyclosporin A in human He La cells. FEBS Leff. 1994- 350: (2−3): 304 308.
- Patchett A.A., White R.F., Goegelman R.F. Method for the production of a modified «8-amino-acid» cyclosporine derivatives U S. US5318901(C1. 435−71.1- c 12 p 21 (04) 07 Jun 1994.
- Peeters H., Zocher R., Kleinkauf H. Synthesis of beauvericin by a multifunctional enzyme. J Antibiotics 1988- 41:3: 352−359.
- Peeters H., Zocher R., Madry N. et al. Cell-free synthesis of the depsipeptide beauvericin. J. Antibiotics 1983- 36: 12: 1762−1766.
- Petcher T.J., Weber H.P., Ruegger A. Crystal and molecular structure of an iodo derivative of the cyclic undecapeptide cyclosporin A. Helv. Chim. Acta 1976- 59: 5: 1480−1488.
- Piontek M., Porschen R. Growth inhibition of human gastrointestinal cancer cells by cyclosporin A. J. Cancer. Res. Clin. Oncology 1994- 120: 12: 695−699.
- Powles R.L., Barrett A.J., Clink H. et al. Cyclosporin A for the treatment of GVH-disease in man. Lancet i i 1978- 1327−1330.
- Quesniaux V.F.J., Schreier M.H., Wenger P.C. et al. Cyclophilin binds to the region of cyclosporine involved in its immunosuppressive activity. Eur. J. Immunol. 1987- 17: 1359−1365.
- Raem G., Cook L., Vilick I. Gamma-interferon synthesis by human thymocytes and T lymphocytes inhibited by cyclosporin. Science1983- 221: 4605: 63−65.
- Reddy G.R. Cloning and characterization of a Plasmodium falciparum cyclophilin gene that is stage-specifically expressed. Med. Biochem. Parasitol. 1995- 73: S: 111−121.
- Rehacek Z. The cyclosporins. Folia Microbiol. 1995- 40: 1: 68−88.
- Reynolds K.A., Wallace K.K., Handa S. et al. Biosynthesis of the shikimate-derived starter unit of the immunosuppressant ascomycin. J. Antibiotics 1997- 50: 8: 701−703.
- Richmond D.V. Effects of toxicants on the morphology and fine structure of fungi. Adv. Appl. Microbiol. 1975- 19: 289−319.
- Richter A., Davies D.E., Alexander P. Growth inhibitory effects of FK 506 and cyclosporin A independent of inhibition of calcineurin. Biochem. Pharmacol. 1995- 49: 3: 367−373.
- Rueg ger A., Kuhn M., Lechti H. Cyclosporin A, ein immunosuppressive wirksamer Peptidmetabolites aus Trichoderma polysporum. Helv. Chim. Acta 1976- 59: 1075−1079.
- Sakamoto K., Izumi S., Miyachi M. et al. A new assay method for immunosuppressants with a tacrolims (FK 506)-like mode of action. J. Antibiotics 1995- 48: 727−729.
- Sakamoto K., Tsuji E., Abe F. FR901483, a novel immunosuppressant isolated from Cladobotryum sp. № 11 231. J. Antibiotics 1996- 49: 1: 37−44.
- Salcedo Fernandes R., Ruiz — Herrera J. Isolation and characterization of a mycelial cytochrome a deficient mutant and the role of mitochondria in dimorphism of Mucor rouxii. Exp. My-col. 1993- 17: 142−154.
- Salturo G.M., Zink D.L., Dahl A. et al. Meridamycin: a novel non immunosuppressive FKBP12 ligand from Streptomyces hygroscopicus. Tetrahedron Lett. 1995- 36: 997−1000.
- Schreider S.L. Chemistry and biology of the immunophilins and their immunosuppressive ligands. Science 1991- 283: 283−287.
- Schutkowski M., Drewello M., Woellum S. et al. Extended binding sites of cyclosporin as revealed by the interaction with HIV-lGag polyprotein derived oligopeptides. FEBS Lett. 1996- 394: 3: 289 294.
- Sedmera P., Havlicek V., Jegorov A. et al. Cyclosporin D Hydroperoxid, a new metabolite of Tolypocladium terricola. Tefrahedron Leff. 1995- 36: 38: 6953−6956.
- Sehgal S.N., Molnar-Kimbler K., Ocaen T.D. et al. Rapamycin: a novel immunosuppressive macrolide. Med. Res. Rev. 1994- 14: 1−22.
- Selva E., Montanini N., Stella S. et al. Targeted screening for elongation factor Tu binding antibiotics. J. Antibiotics 1997- 50: 1: 2226.
- Shaw K.T.-Y., Ho A.M., Raghavan A. et al. Immunosuppressive drugs prevents a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells. Proc. Nat. Acad. Sci. USA 1995- 92: 24: 111 205−111 209.
- Speeg K.V., Maldonado H.L. Effect of nonimmunosuppressive cyclosporin analog SDZ PSC833 on colchicine and doxorubicin biliary secretion by the rat in vivo. Cancer Chemother. Pharmacol. 1994- 34: 2: 133−136.
- Stapf V., Thalhammer T., Huber-Huber R. et al. Inhibition of rhodamine 123 secretion by cyclosporin A as a model of P-glycoprotein mediated transport in liver. Anticancer Res. 1994- 14: 2A: 581−585.
- Sweet P., Chan P.K., Slater L. M. Cyclosporin A and verapamil enhancement of daunorubicin-produced nuclear protein B23 translocation in daunorubicin-resistant and sensitive human and murine tumor cells. Cancer Res. 1989- 49: 3: 677−680.
- Takahashi M., Iwasaki S., Kobayashi H. et al. Studies on macrocyclic lacton antibiotics. XI. Antimitotic and antubular activity of new antitumour antibiotics, rhizoxins and its homologues. J. Antibiotics 1987- 40: 66−72.
- Takahashi N., Hayano T., Suzuki M., Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Nature 1989- 337: 6206: 473−475.
- Takamatsu S., Kim Y.-P., Komiya T. et al. Chlovalicin, a new cytocidal antibiotic produced by Sporothrix sp. FO 4649 II. Physico-chemical properties and structure elucidation. J. Antibiotics 1996- 49: 7: 635−643.
- Tanaka H., Kuroda A., Marusawa H. Structure of FK506: a novel immunosuppressant isolated from a Streptomyces. J. Am. Chem. Soc. 1987- 109: 5031−5039.
- Teague S.J., Cooper M.E., Stocks M.J. Synthesis of FK506 -cyclosporin hybrid macrocycles. Bioorg. Med. Chem. Lett. 1995- 5: 20: 2341−2346.
- Thali M. Cyclosporins: immunosuppressive drugs with antifflV-1 activity. Mol.Med. Today 1995- 1: 6: 287−291.
- Thomson A., Webster L.M. The influence of cyclosporin A on cell-mediated immunity. Clin.Exp.Immunology 1988- 71: 3: 369−376.
- Tillement J.P., Albengres E. Cyclosporin A and ketokonazole: drug interaction or therapeutic combinations? Therapie 1995- 50: 3: 185 189.
- Tocci M. J., Matkovich D. A., Collier K.A. et al. The immunosuppressant FK506 selectively inhibits expression of early T cells activation genes. J. Immunology 1989- 143: 2: 718−726.
- Traber R., Kuhn M., Loosli H.R. et al. Neue Cyclopeptide aus Trichoderma polysporum (Link ex Pers.) die Cyclosporine B, D, und E. Helv.Chim. Acta 1977- 60: 1568−1573.
- Traber R., Kuhn M., Ruegger A. et al. Die Structur von Cyclosporin C. Helv. Chim. Acta 1977- 60: 1247−1248.
- Traber R., Loosli H., Hofmann H. et al. Isolierung und Structur Vermittlung der neuen Cyclosporine E, F, G, H und I. Helv. Chim. Acta 1982- 65: 1655−1657.
- Twentyman P.R., Fox N.E., White D.J.G. Cyclosporin A and its analogues as modifiers of adriamycin and vincristine resistance in a multidrug resistant human lung cancer cell line. Brit. J. Cancer 1987- 56: 1:55−57.
- Vayuvegula B., Slater L., Meador J. et al. Correction of altered membrane potentials. A possible mechanism of cyclosporin A and verapamyl reversal of pleiotropic drug resistance in neoplasia. Cancer Chemother. Pharmacol. 1988- 22: 2: 163−168.
- Vezina C., Kudelski A., Sehgal S.N. Rapamycin (AY22,989)a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J. Antibiotics 1975- 28: 721−726.
- Waldimarsson H. Mechanism of action of cyclosporin A. J. Immunol. Today 1994- 15: 5: 247.
- Wallace K.K., Reynolds K.A., Koch H.P. et al. Biosynthetic studies of ascomycin (FK520). J. Am. Chem. Soc. 1994- 116: 1 160 011 601.
- Wartburg A., Traber R. Chemistry of the Natural cyclosporine metabolites. Progress in Allergy 1986- 38: 28−32.
- Weber G., Leither E. Disruption of the cyclosporine synthetase gene of Tolypocladium niveum. Curr. Genet. 1994- 26: 5−6: 461−467.
- Weillette A., Boorman M.A., Horak E.M. et al. The CD4 and CD8 T cell surface antigen are associated with the internal membrane tyrosin-protein kinase p56 lck Cell 1988- 55: 301−308.
- Wenger R.M. Chemistry of cyclosporin. In: Cyclosporin A. Amsterdam Elsevier Biomed 1989- 19−29.
- Wenger R.M. Cyclosporine and analogues: structural requirements for immunosuppressive activity. Transplantant. Proc. 1986- 18: 6: Suppl. 5: 213−218.
- Wenger R.M. Pharmacology of cyclosporin (Sandimmune). II. Chemistry Pharmacol. Rev. 1989- 41: 3: 243−247.
- Wenger R.M. Synthesis of cyclosporin. Helv. Chim. Acta 1983- 66: 2672−2676.
- Wenger R.M. Synthesis of cyclosporin and analogues. Structure activity relationships of new cyclosporine derivatives. Transplant. Proc. 1983- 15: 4: 2230−2234.
- Wenger R.M. Synthesis of enantiomerically pure (2S, 3R, 4R, 6E)-3-hydroxy-4-methyl-2-methylamino-6-octenoic acid startingfrom tartaric acid. Helv. Chim. Acta 1983- 66: 7: 2308−2321.
- Wenger R.M., Payne T.G., Schreier M.H. Cyclosporine: chemistry, structure activity relationships and mode of action. Prog. Clin. Biochem. Med. 1986- 3:157−191.
- Wiesenger D., Borel J.F. Studies on the mechanism of action of cyclosporin A. Immunobiol. 1979- 156: 454−459.
- Wong G.K., Grifith S., Kojimo I. et al. Antifungal activities of rapamycin and it derivatives prolylrapamycin, 32-desmethylrapamycin and 32-desmethoxyrapamycin. J. Antibiotics 1998- 51:5: 487−491.
- Wood M.A., Bierer B.E., Rapamycin: biological and therapeutic effects, bindings by immunophilins and molecular targets of action. Perspect. Drug Discovery Dis. 1994- 2: 1: 163−184.
- Yamamoto K., Kurokawa N., Kadobayashi M. et al. Mapping of cyclosporin A binding sites in cyclophilin A by using synthetic peptides. Regul.Pept. 1995- 59: 1: 23−30.
- Zeder-Lotz G., Van Regenmortel M.H.V., Wenger R. et al. Interaction of cyclosporin analogs with cyclophilin: relationship between structure and binding. J. Chromatogr., B: Biomed. Appl. l994−662: 2: 301−306.
- Zenke G., Baumann G., Wenger R. et al. Molecular mechanisms of immunosuppression by cyclosporin. Ann. N.Y. Acad. Sci. 1993- 685: 330−335.
- Zhu D., Cardenas M.E., Heitman J. Myristoylation of calcineurin B is not required for function or interaction with immunophilin immunosuppressant complexes in the yeast Saccharomyces cerevisiae. J.Biol. Chem. 1995- 270: 42: 24 831−24 838.
- Zocher R., Keller U., Kleinkauf H. Enniatin synthetase, a novel type of multifunctional enzyme catalizing depsipeptide synthesis in Fusarium oxysporum. Biochemistry 1982- 21: 1: 43−48.
- Zocher R., Keller U., Kleinkauf H. Mechanism of depsipeptide formation catalyzed by enniatin synthetase. Bioch. Bioph. Res. Commun. 1983- 110: 1: 292−299.
- Zocher R., Kleinkauf H. Biosynthesis of enniatin B: partial purification and characterization of synthesizing enzyme and studies of the biosynthesis. Bioch. Bioph. Res. Commun. 1978- 81: 4: 1162−1167.
- Zocher R., Madry N., Peeters H. et al. Biosynthesis of cyclosporin A. Phytochemistry 1984- 23: 549−555.
- Zocher R., Nihira T., Paul E. et al. Biosynthesis of cyclosporin A: partial purification and properties of a multi-functional enzyme from Tolypocladium inflatum. Biochemistry 1986- 25: 3: 550−562.