Shortpeptidesbasedonthetripeptides,Leu-Arg-ProandLeu-Lys-Pro,weresynthesizedbymicrowaveassistedsolid-phasesynthesismethod,inordertomakeasearchforpotentialinhibitorsforangiotensinI-convertingenzyme(ACE)withminimumsideeffectsinthetreatmentofhypertension.OnepeptidewiththesequenceLeu-Arg-Pro-Phe-PheshowsthestrongestinhibitiontowardsACEwithanIC50valueof0.26μmol/Linvitro.Thestudyofstructure-activityrelationshipshowsthattheintroductionofabulkygroupintotheN-terminalofthisseriesofinhibitorsmayenlargesterichindrance,resultinginthepoorinhibitoryactivitytowardsACE.TheinhibitoryactivitydecreasedinturnwhenL-Pro,D-ProorAc6cwasattheC-terminalrespectively.ThebindinginteractionbetweeneachoftheseinhibitorsandtesticularACE(tACE)wasperformedbymoleculardocking.TheresultssuggestthatLeu-Arg-Pro-Phe-PhemainlyoccupiedtheS1subsiteoftACE,andmadecontactwithtACEviasevenH-bonds.ItappearedthatthesiteonthepeptidethatboundwithtACEwasinfluencedbytheconfigurationoftheaminoacid,LorD-form,attheC-terminalofthepeptide.
