Epicypher, Inc. — Department of Health and Human Services SBIR Phase II: 400
Epicypher, Inc. — SBIR Phase II award from Department of Health and Human Services.
- Amount
- $1,499,995
- Agency
- Department of Health and Human Services · National Institutes of Health
- Program / Phase
- SBIR · Phase II
- Topic
- 400
- Solicitation
- PA16-302
- NAICS
- —
- Place of performance
- NC
- Period
- 2017-08-01 → 2019-07-31
Description
PROJECT SUMMARYEpigeneticregulatorsrepresentanewfrontierindrugdiscoveryandarerapidlyattractingpharmaceuticalinterestsduetotheirremarkabledruggabilityandstrongconnectionwithhumandiseasese gmetabolicsyndromesneurodegenerativedisordersandcancersTodatetheepigenomeconsistsofoverknownproteinsHoweververyfewepigeneticmodifiersarebeingpursuedindrugdevelopmentprograms due to our limited understanding of what proteins these enzymes regulateThis narrow saturation oftheepigeneticdrugarenaisfueledbyadearthoftoolstosystematicallyidentifyandcharacterizepotentialtargetsTo aid in the discovery of novel relationships between enzymes and the proteins that they targetwe willcommercializehighcomplexityorientedpeptidearraylibrariesOPALsInPhaseIstudieswesynthesizedOPALlibrariescomprisingacorearginineROPALorlysineKOPALresiduewithflankingdegeneratesequencesoraminoacidsinbothNandCterminaldirectionsFigureanddemonstratedthatOPALsarepowerfultoolstosystematicallycharacterizetargetmotifsofwriterenzymesOurfocushereistodevelop OPALs to examinewriterenzymes that modify lysine or arginine residuesIn Phase IIEpiCypher willscale up synthesis of the unmodified KOPAL and ROPAL peptide libraries and optimize a highthroughputwell assay format for validation using methyltransferase assays developed in the Phase I studiesAimWewillalsovastlyexpandthecommercialutilityofourdiscoveryplatformontwofrontsdevelopinganonradioactive detection system and a userfriendly data analysis pipeline establishingAimandexpandingour KOPAL platform to analyze lysineacylation writer enzymesAimSeven additional lysinemodified acylgroupposttranslationalmodificationsofwhichacetylationisafoundingmemberhavebeenrecentlyidentifiede gcrotonylationbutyrylationor propionylationwhich function together with lysine acetylation toregulategeneactivationGiventhewelldescribedroleofhistoneacetylationindiseasethesenewacylationPTMsrepresentanexcitingnewfieldofepigeneticstudythathasgreatdrugdevelopmentpotentialTheinnovativediscoveryplatformdescribedhereinprovidesthefirstcomprehensivescreeningtooltostudyepigeneticwriterenzymesEpiCypherhasassembledastrongscientificteamconsistingofpioneersinthefieldofepigeneticregulationDrsMarkBedfordandScottRothbartanddetectionchemistryDrMarceyWaterstodeveloparobustversatileanduserfriendlydiscoveryplatformthatwillhaveapowerfultranslational impact on epigenetic research and therapeutic development