BEGIN:VCALENDAR VERSION:2.0 PRODID:-//132.216.98.100//NONSGML kigkonsult.se iCalcreator 2.20.4// BEGIN:VEVENT UID:20260606T234653EDT-0401pS2zuS@132.216.98.100 DTSTAMP:20260607T034653Z DESCRIPTION:Dr. Youla S. Tsantrizos\nAssociate Professor\nChemical Biology and Medicinal Chemistry\nChemistry Department\nԹ\n“In Sili co Design and Parallel Synthesis of Active-Site\nInhibitors of the Human F arnesyl Pyrophosphate Synthase”\n \nThe human farnesyl pyrophosphate synth ase (hFPPS) is responsible\nfor the catalytic elongation of dimethylallyl pyrophosphate to\ngeranyl pyrophosphate and then to farnesyl pyrophosphate (FPP) via\nthe successive condensation of two isopentenyl pyrophosphate\n units.  Post-translational prenylation with FPP of various\nproteins is cr ucial to their biological role.  It is estimated\nthat over 60 human prote ins are farnesylated and this modification\nconfers membrane localization\ , promotes specific protein-protein\ninteractions and plays a critical rol e in intracellular trafficking\nand signal transduction.  Addition of the FPP lipidic moiety\nto the small GTP-binding proteins Ras is also required in order to\nregulate the proliferation\, invasive properties\, and pro-a ngiogenic\nactivity in human cancers.  Current therapeutic drugs that\ninh ibit hFPPS (such as risedronate and zoledronate) are used to\ntreat osteop orosis and bone cancer metastasis. A characteristic\npharmacophore of all these drugs is a bisphosphonate moiety\, which\nserves as the key anchor i n the binding interactions with\nenzyme.  However\, this structural motif is also responsible\nfor the low oral bioavailability and high accumulatio n into bone\ntissue that is observed with this class of compounds.  Our\ng oal is to design more selective inhibitors with significantly\nreduced dep endency on a bisphosphonate moiety for binding into the\nactive site of hF PPS.  A structure-based approach has been\npursued in designing novel inhi bitors of hFPPS\, guided by X-ray\ncrystallography and in silico screening using GLIDE®.  The\ndevelopment of synthetic methodologies that permit th e parallel\nsynthesis of structurally diverse compounds and the biological \nactivity of these compounds will be reported.\n DTSTART:20100510T160000Z DTEND:20100510T160000Z LOCATION:McIntyre Medical Building\, CA\, QC\, Montreal\, H3G 1Y6\, 3655 pr omenade Sir William Osler SUMMARY:Biochemistry Seminar Dr. Youla Tsantrizos URL:/channels/event/biochemistry-seminar-dr-youla-tsan trizos-116936 END:VEVENT END:VCALENDAR