《生物技术药物》之重组多肽、蛋白质类激素药物课件

各论五重组多肽、蛋白质类激素药物激素(hormone)由腺体合成和释放，通过循环系统，作用于靶细胞周倜的微量化学信号分子。特点：内分泌信号调节系统，作用远距离靶细胞。包括两类：含氮激素和甾体激素。含氮激素：胰岛素、胰高血糖素、生长素、促性腺激素等。受体类型：胰腺B细胞(70%)A细胞(20%)D细胞(10%)Theinsulinreceptor(IR)isatransmembranereceptorthatisactivatedbyinsulin,IGF-I,IGF-IIandbelongstothelargeclassoftyrosinekinasereceptors。Effectofinsulinonglucoseuptakeandmetabolism.Insulinbindstoitsreceptor(1),which,inturn,startsmanyproteinactivationcascades(2).Theseinclude:translocationofGlut-4transportertotheplasmamembraneandinfluxofglucose(3),glycogensynthesis(4),glycolysis(5),andfattyacidsynthesis(6).Somatostatin(alsoknownasgrowthhormone-inhibitinghormone(GHIH)orsomatotropinrelease-inhibitingfactor(SRIF))orsomatotropinrelease-inhibitinghormone.apeptidehormonethatregulatestheendocrinesystemandaffectsneurotransmissionandcellproliferationviainteractionwithGprotein-coupledsomatostatinreceptorsandinhibitionofthereleaseofnumeroussecondaryhormones.SuppressesthereleaseofpancreatichormonesInhibitsinsulinreleasewhensomatostatinisreleasedfromdeltacellsofpancreasInhibitsthereleaseofglucagonGlucagonreceptor,aGprotein-coupledreceptorThealphasubunitspecificallyactivatesthenextenzymeinthecascade,adenylatecyclase.人生长激素Humangrowthhormone在脑垂体前叶合成191个氨基酸，单链，两个二硫键受体：生物学特性：促进蛋白质合成促进软骨细胞增殖影响糖多谢临床：生长激素缺乏症GH受体：受体酪氨酸激酶GHexertssomeofitseffectsbybindingtoreceptorsontargetcells,whereitactivatestheMAPK/ERKpathway.ThroughthismechanismGHdirectlystimulatesdivisionandmultiplicationofchondrocytesofcartilage.GHalsostimulates,throughtheJAK-STATsignalingpathway,theproductionofinsulin-likegrowthfactor1(IGF-1).促性腺激素类药物Gonadotropins(orglycoproteinhormones)Gonadotropins(orglycoproteinhormones)areproteinhormonessecretedbygonadotropecellsoftheanteriorpituitaryofvertebrates.Thisisafamilyofproteins,whichincludethemammalianhormonesfollicle-stimulatinghormone(FSH),luteinizinghormone(LH),placentalchorionicgonadotropinshCGandeCG[4]andchorionicgonadotropin(CG),aswellasatleasttwoformsoffishgonadotropins.Thesehormonesarecentraltothecomplexendocrinesystemthatregulatesnormalgrowth,sexualdevelopment,andreproductivefunction.ThehormonesLHandFSHaresecretedbytheanteriorpituitarygland,whilehCGandeCGaresecretedbytheplacenta.GonadotropinreceptorsareembeddedinthesurfaceofthetargetcellmembranesandcoupledtotheG-proteinsystem.SignalstriggeredbybindingtothereceptorarerelayedwithinthecellsbythecyclicAMPsecondmessengersystem.卵泡刺激素follicle-stimulatinghormone(FSH)alpha亚基92个

氨基酸和beta亚基111个氨基酸N端糖基化，以链间二硫键连接生物学特性：男/女男女follicle-stimulatinghormone(FSH)Follicle-stimulatinghormone(FSH)isahormonefoundinhumansandotheranimals.Itissynthesizedandsecretedbygonadotrophsoftheanteriorpituitarygland.FSHregulatesthedevelopment,growth,pubertalmaturation,andreproductiveprocessesofthebody.FSHandluteinizinghormone(LH)actsynergisticallyinreproduction.Specifically,anincreaseinFSHsecretionbytheanteriorpituitarycausesovulation.FSHregulatesthedevelopment,growth,pubertalmaturation,andreproductiveprocessesofthehumanbody.Inbothmalesandfemales,FSHstimulatesthematurationofgermcells.Inmales,FSHinducesSertolicellstosecreteinhibinandstimulatestheformationofsertoli-sertolitightjunctions(zonulaoccludens).Infemales,FSHinitiatesfolliculargrowth,specificallyaffectinggranulosacells.WiththeconcomitantriseininhibinB,FSHlevelsthendeclineinthelatefollicularphase.Thisseemstobecriticalinselectingonlythemostadvancedfollicletoproceedtoovulation.Attheendofthelutealphase,thereisaslightriseinFSHthatseemstobeofimportancetostartthenextovulatorycycle.LikeitspartnerLH,FSHreleaseatthepituitaryglandiscontrolledbypulsesofgonadotropin-releasinghormone(GnRH).Thosepulses,inturn,aresubjecttotheoestrogenfeed-backfrom