Scott Miller
Sterling Professor of ChemistryCards
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Professor
Department Chair
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Titles
Sterling Professor of Chemistry
Professor; Department Chair
Biography
Dr. Miller's laboratory is focused on the creation of new catalysts for complex molecule synthesis and derivatization. Historically, the Miller Lab has endeavored to develop peptide-based catalysts for enantioselective reactions. They have also attempted to bring the principles of asymmetric catalysis into areas of other types of selective synthesis (e.g., regioselectivity, site-selectivity and chemoselectivity), with a particular focus on natural product diversification. They focus on molecular functionality that is ubiquitous in complex natural products, thus allowing these naturally occurring materials to be used as scaffolds for new bioactive entity synthesis. In orthogonal projects, the Miller Lab has developed catalysts for many enantioselective reactions, with a focus on unusual and biochemically relevant aspects of stereochemistry.
The Miller Lab's focus for catalyst development has been on peptide-based catalysts. The catalysts they generate have therefore allowed for a consideration of mechanistic analogies to enzymes. This strategy has also enabled optimization of the catalysts with the development of a range of combinatorial methods for catalyst screening.
Last Updated on April 07, 2025.
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Chemistry
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Overview
Synthesis and Derivation of Complex Molecules; Stereochemistry; Atropisomerism
ORCID
0000-0001-7817-1318
Research at a Glance
Yale Co-Authors
Frequent collaborators of Scott Miller's published research.
Publications Timeline
A big-picture view of Scott Miller's research output by year.
Julie Zimmerman
145Publications
4,285Citations
Publications
2025
Chemical and ribosomal synthesis of atropisomeric and macrocyclic peptides with embedded quinolines
Knudson I, Dover T, Dilworth D, Paloutzian C, Paz O, Lin J, Cho H, Gonen T, Schepartz A, Miller S. Chemical and ribosomal synthesis of atropisomeric and macrocyclic peptides with embedded quinolines. Nature Chemistry 2025, 1-12. PMID: 40962910, DOI: 10.1038/s41557-025-01935-4.Peer-Reviewed Original ResearchCitationsAltmetricConceptsComplex natural productsMedicinal chemistry optimizationNatural productsAtropisomeric axisMacrocyclic architecturesChemical spacePeptide macrocyclesChemistry optimizationQuinoline pharmacophorePeptide backboneMacrocyclic peptidesB-ketoLinear peptidesTherapeutically relevant targetsQuinolineConformance controlChemical complexityPeptide ligandsBiarylMacrocycleNon-canonical amino acidsPharmacophoreDerivatizationAmideLigandSite-selective protein editing by backbone extension acyl rearrangements
Roe L, Piper I, Schissel C, Dover T, Shah B, Hamlish N, Garapaty A, Zheng S, Dilworth D, Wong N, Zhang Z, Chatterjee A, Francis M, Miller S, Schepartz A. Site-selective protein editing by backbone extension acyl rearrangements. Nature Chemical Biology 2025, 21: 1621-1630. PMID: 40841495, DOI: 10.1038/s41589-025-01999-w.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAcyl rearrangementAminoacyl-tRNA synthetase enzymesA-hydroxy acidsGenetic code expansionGenetically encoded proteinsIntramolecular rearrangementAminoacyl-tRNASide chainsPost-translationallySynthetase enzymesCode expansionAcid monomersNext-generation approachPotential materialNucleophilesMonomerProteinBackboneRearrangementIn vivoHeteropolymersCellsPolypeptideMaterialsGeneticsFurther Confirmation of the Structure of 3′-(2-Pyridyldithio)-3′-deoxyadenosine and 3′-Thio-3′-deoxyadenosine: Synthetic Convergence with Cordycepin
Dover T, Robins J, Mercado B, Schepartz A, Miller S. Further Confirmation of the Structure of 3′-(2-Pyridyldithio)-3′-deoxyadenosine and 3′-Thio-3′-deoxyadenosine: Synthetic Convergence with Cordycepin. The Journal Of Organic Chemistry 2025, 90: 9295-9299. PMID: 40557811, DOI: 10.1021/acs.joc.5c00954.Peer-Reviewed Original ResearchAltmetricSelective Oxidation of Disparate Functional Groups Mediated by a Common Aspartic Acid-Based Peptide Catalyst Platform
Huth S, Stone E, Miller S. Selective Oxidation of Disparate Functional Groups Mediated by a Common Aspartic Acid-Based Peptide Catalyst Platform. Accounts Of Chemical Research 2025, 58: 2072-2087. PMID: 40530828, PMCID: PMC12226787, DOI: 10.1021/acs.accounts.5c00247.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsPeptide catalystsMedicinally relevant moleculesPeptide-based catalystsBaeyer-Villiger oxidationAsp peptidesSynthetic reaction conditionsSynthetically relevant transformationsComplex natural productsNatural productsAsymmetric catalysisCatalyst platformStoichiometric oxidantOxygen atomsSelective oxidationNoncovalent interactionsReaction conditionsBioactive natural productsBioactive analoguesMolecular scaffoldsCatalystFunctional groupsDrug analoguesPeptide sequencesRelevant moleculesDrug moleculesCatalyst-Controlled Site-Selective and Epimer-Selective Hydrogenations of Thiostrepton
Peterson P, Mercado B, Miller S. Catalyst-Controlled Site-Selective and Epimer-Selective Hydrogenations of Thiostrepton. Journal Of The American Chemical Society 2025, 147: 17161-17169. PMID: 40358225, PMCID: PMC12126753, DOI: 10.1021/jacs.5c02720.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPhosphoramidite ligandAsymmetric hydrogenation methodMonodentate phosphoramidite ligandsStereoselectivity of reductionX-ray crystallographyStudies of ligandsModel substrateProtecting-groupLigand chiralityLigand scaffoldStereochemical outcomeAbsolute stereochemistryMild conditionsMultidimensional nuclear magnetic resonance methodsNuclear magnetic resonance methodsDehydroalanine residueHydrogenation methodLigandX-rayHydrogenStereoisomersStereochemistryControlled formationStericallyMagnetic resonance methodsEnantioselective Hydrodifluoroalkylation of Alkenes with Conformationally Tuned Peptidyl Hydrogen Atom Transfer Catalysts
Pereira M, Geunes E, Shao H, Zhang Y, Cheng J, Magpantay S, Mercado B, Mayer J, Houk K, Knowles R, Miller S. Enantioselective Hydrodifluoroalkylation of Alkenes with Conformationally Tuned Peptidyl Hydrogen Atom Transfer Catalysts. Journal Of The American Chemical Society 2025, 147: 11412-11424. PMID: 40111502, PMCID: PMC11983094, DOI: 10.1021/jacs.5c01166.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsHydrogen atom transferHydrogen atom transfer catalystCarbon-carbon bond formationX-ray crystallographic analysisCarbon-centered radicalsChiral catalystsAsymmetric inductionAtom transferDFT calculationsPhotocatalytic generationTransfer catalystCrystallographic analysisBond formationEnantiomeric ratioCatalystX-rayAlkenesRadicalsDFTTrialkylaminesAmideConformationCysteineTetrapeptideResiduesCatalyst-Controlled Regiodivergent Oxidation of Unsymmetrical Diols
Zacate S, Rein J, Rozema S, Annor R, Miller S, Lin S. Catalyst-Controlled Regiodivergent Oxidation of Unsymmetrical Diols. Journal Of The American Chemical Society 2025, 147: 8118-8124. PMID: 40019207, PMCID: PMC11918261, DOI: 10.1021/jacs.5c00330.Peer-Reviewed Original ResearchCitationsAltmetricBPS2025 - β-amino acids reduce ternary complex stability and alter the translation elongation mechanism
Navarrete F, Griffin W, Chan Y, Martin M, Amaya J, Brady R, Natchiar K, Knudson I, Altman R, Schepartz A, Miller S, Blanchard S. BPS2025 - β-amino acids reduce ternary complex stability and alter the translation elongation mechanism. Biophysical Journal 2025, 124: 83a-84a. DOI: 10.1016/j.bpj.2024.11.513.Peer-Reviewed Original ResearchBPS2025 - β-Amino acids reduce ternary complex stability and alter the translation elongation mechanism
Navarrete F, Griffin W, Chan Y, Martin M, Amaya J, Brady R, Natchiar K, Knudson I, Altman R, Schepartz A, Miller S, Blanchard S. BPS2025 - β-Amino acids reduce ternary complex stability and alter the translation elongation mechanism. Biophysical Journal 2025, 124: 171a. DOI: 10.1016/j.bpj.2024.11.930.Peer-Reviewed Original ResearchThioesters Support Efficient Protein Biosynthesis by the Ribosome
Kent A, Robins J, Knudson I, Vance J, Solivan A, Hamlish N, Fitzgerald K, Schepartz A, Miller S, Cate J. Thioesters Support Efficient Protein Biosynthesis by the Ribosome. ACS Central Science 2025, 11: 404-412. PMID: 40161951, PMCID: PMC11950863, DOI: 10.1021/acscentsci.4c01698.Peer-Reviewed Original ResearchCitationsAltmetricConceptsProtein biosynthesisIn vitro translation reactionsCCA-adding enzymeEfficient protein biosynthesisAminoacyl-tRNA synthetasesTranslation machineryTranslation reactionsThioester intermediateRibosomeBiochemical reactionsEffective substrateThioesterBiosynthesisA-amino acidsTruncated tRNAsTRNATRNAsPeptide synthesisPolymer synthesisOxo-esterPrebiotic peptide synthesisSynthetaseXyloseExchange reactionFlexizymes
Academic Achievements & Community Involvement
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Activities
activity Synthesis and Study of Organocatalysts Tethered to Dendronized Polymer Support
01/01/2009 - 01/01/2013ResearchDetailsIsrael; United StatesAbstract/SynopsisWe are trying to develop a new class of catalysts for synthetic chemistry that are based on simple organic molecules that are immobilized on dendritic polymer supports. These studies have fundamental value in that they may unveil new effects that are specific to a polymeric scaffold. Catalysts may also offer improved efficiency and recyclability which has advantages for reducing environmental impacts. URL: http://onlinelibrary.wiley.com/doi/10.1002/chem.201102474/abstract
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