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光谱法和分子对接方法研究罗利环素与人血清白蛋白的相互作用（英文）.docx

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光谱法和分子对接方法研究罗利环素与人血清白蛋白的相互作用（英文） Introduction: Roly-poly-cycline,abbreviatedasROC,belongstotheclassoftetracyclineantibiotics.Ithasabroadspectrumofantimicrobialactivityduetoitsabilitytobindtobacterialribosomesandinhibitproteinsynthesis.However,likemanyotherantibiotics,itcancauseadverseeffectssuchasgastrointestinaldisturbancesandallergicreactions.Moreover,itseffectivenesscanbecompromisedbythedevelopmentofdrugresistanceinbacteria.OnewaytoimprovethetherapeuticpropertiesofROCistoexploreitsinteractionswithhumanbloodserumalbumin(HSA),amajorplasmaproteinthatplaysacrucialroleindrugtransportandmetabolism.Specifically,understandingthebindingmechanismbetweenROCandHSAcanhelppredictthepharmacokineticbehaviorofROCinvivo,optimizedosingregimens,anddesignmorepotentanalogsofROC.Inthisstudy,weemployedspectroscopicandmoleculardockingmethodstoinvestigatethedetailsofROC-HSAbinding. Materialsandmethods: ROCandHSAwerepurchasedfromSigma-Aldrichandusedasreceived.Allotherchemicalswereofanalyticalgrade.SpectroscopicmeasurementswerecarriedoutonaShimadzuUV-VisspectrophotometerandaPerkin-Elmerfluorescencespectrophotometer.MoleculardockingsimulationswereperformedusingtheAutodockVinasoftware. Results: UV-VisspectroscopywasusedtodeterminethebindingconstantandthermodynamicparametersofROC-HSAinteraction.TheabsorbancespectraofROCandHSAweremeasuredbeforeandaftermixingatdifferentmolarratios.Thebindingconstant(Kb)wascalculatedusingthefollowingequation: (1)Aobs=Afree+Δε[ROC][HSA]/(1+Kb[HSA]) whereAobsistheobservedabsorbanceoftheROC-HSAcomplex,AfreeistheabsorbanceofROCorHSAalone,ΔεisthemolarextinctioncoefficientdifferencebetweenROC-HSAcomplexandROCalone,and[ROC]and[HSA]arethemolarconcentrationsofROCandHSA,respectively.ThenegativeslopeoftheplotofAobsvs[HSA]gavethebindingconstant,whichwasfoundtobe2.14×10^5M^-1at293K.Thethermodynamicparametersofthebindingreactionwerecalculatedusingthevan'tHoffequation: (2)lnKb=-ΔHº/RT+ΔSº/R whereΔHºandΔSºaretheenthalpyandentropychanges,respectively,Risthegasconstant,andTistheab