About

Dr. Christopher J. Evans received his Ph.D. from Imperial College London, where he conducted thesis research on endorphins and enkephalins at the Medical Research Council Institute in Mill Hill. Following his doctoral studies, he completed a postdoctoral fellowship at Stanford University. His research accomplishments include the identification of several novel endogenous opioid peptides and the cloning of the first opioid receptor. Dr. Evans joined the UCLA faculty in the Department of Psychiatry and Biobehavioral Sciences, where he has contributed significantly to the field of neuropharmacology. He served as Director of the UCLA Brain Research Institute from 2004 to 2017 and is the Stefan Hatos Professor, directing the Shirley and Stefan Hatos Center for Neuropharmacology in the UCLA Semel Institute. Additionally, he is the director of the NIH-funded Center for Opioid Receptors and Drugs of Abuse (CSORDA), which has maintained continuous NIH funding for over 30 years. His research focuses on understanding the action of opioid drugs such as morphine and heroin at molecular, cellular, and behavioral levels.

Research topics

• Chemistry
• Organic chemistry
• Stereochemistry
• Chromatography
• Biology
• Biochemistry
• Combinatorial chemistry

Selected publications

• De Novo Design of Enantioselective Artificial Metalloenzyme Photocatalysts Containing Metal Polypyridine Cofactors

  ChemRxiv · 2026-05-07

  articleOpen access

  The ability to create protein scaffolds that impart enantioselectivity to simple, readily available metal catalysts could redefine the landscape of asymmetric catalysis. Artificial metalloenzymes (ArMs), hybrid catalysts that combine a synthetic metal cofactor with a protein scaffold, offer a potential means to achieve this goal, but scaffold discovery has remained constrained by trial-and-error approaches and the functional limits of extant proteins. In this study, we show that generative protein design can be harnessed to create de novo scaffolds that selectively accommodate one enantiomer of a metal polypyridine photocatalyst as a cofactor. The resulting ArMs enable efficient, enantioselective photocatalysis, highlighting a broadly applicable route for programming stereocontrol into metalloenzyme catalysts. High total turnover numbers are achieved, the ArMs can be recycled by simply extracting reaction products and reusing the aqueous ArM solution for subsequent reactions, and even commercially available racemic cofactor can be used for ArM formation. Transient Absorption characterization revealed that improvements to catalysis result from the increased quantum yield and excited state lifetime of the cofactor upon binding and substrate binding proximal to the cofactor within the ArM active site, which controls reaction stereoselectivity and the mechanism of energy transfer involved in photocatalysis. The simplicity of this approach could help transition ArM research out of a small group of specialist labs to any capable of expressing synthetic genes and working with commercially available metal complexes.

  PublisherDOI

• Correction to “Sebetralstat (KVD900): A Potent and Selective Small Molecule Plasma Kallikrein Inhibitor Featuring a Novel P1 Group as a Potential Oral On-Demand Treatment for Hereditary Angioedema”

  Journal of Medicinal Chemistry · 2025-10-30

  articleOpen access
  PublisherDOI

• De novo design of luciferases using deep learning

  Nature · 2023 · 443 citations

  • Chemistry
  • Combinatorial chemistry
  • Biochemistry

  ) comparable to that of native luciferases, but a much higher substrate specificity. The creation of highly active and specific biocatalysts from scratch with broad applications in biomedicine is a key milestone for computational enzyme design, and our approach should enable generation of a wide range of luciferases and other enzymes.

  PublisherOA PDFDOI

• Cascade Synthesis of Fluorinated Spiroheterocyclic Scaffolding for Peptidic Macrobicycles

  Journal of the American Chemical Society · 2023-07-13 · 11 citations

  article

  Octafluorocyclopentene (OFCP) engages linear, unprotected peptides in polysubstitution cascades that generate complex fluorinated polycycles. The reactions occur in a single flask at 0-25 °C and require no catalysts or heavy metals. OFCP can directly polycyclize linear sequences using native functionality, or fluorospiroheterocyclic intermediates can be intercepted with exogenous nucleophiles. The latter tactic generates molecular hybrids composed of peptides, sugars, lipids, and heterocyclic components. The platform can create stereoisomers of both single- and double-looped macrocycles. Calculations indicate that the latter can mimic diverse protein surface loops. Subsets of the molecules have low energy conformers that shield the polar surface area through intramolecular hydrogen bonding. A significant fraction of OFCP-derived macrocycles tested show moderate to high passive permeability in parallel artificial membrane permeability assays.

  PublisherDOI

• Extended β-Strands Contribute to Reversible Amyloid Formation

  ACS Nano · 2022-02-08 · 29 citations

  articleOpen access

  The assembly of proteins into fibrillar amyloid structures was once considered to be pathologic and essentially irreversible. Recent studies reveal amyloid-like structures that form reversibly, derived from protein low-complexity domains which function in cellular metabolism. Here, by comparing atomic-level structures of reversible and irreversible amyloid fibrils, we find that the β-sheets of reversible fibrils are enriched in flattened (as opposed to pleated) β-sheets formed by stacking of extended β-strands. Quantum mechanical calculations show that glycine residues favor extended β-strands which may be stabilized by intraresidue interactions between the amide proton and the carbonyl oxygen, known as C5 hydrogen-bonds. Larger residue side chains favor shorter strands and pleated sheets. These findings highlight a structural element that may regulate reversible amyloid assembly.

  PublisherOA PDFDOI

• Analysis of laboratory-evolved flavin-dependent halogenases affords a computational model for predicting halogenase site selectivity

  Chem Catalysis · 2022-08-09 · 23 citations

  articleOpen access
  PublisherOA PDFDOI

• Analysis of Laboratory-Evolved Flavin-Dependent Halogenases Affords a Computational Model for Predicting Halogenase Site Selectivity

  ChemRxiv · 2022-02-16 · 5 citations

  preprintOpen access

  Flavin-dependent halogenases catalyze selective halogenation of electron-rich aromatic compounds without the need for harsh oxidants required by conventional oxidative halogenation reactions. Predictive models for halogenase site selectivity would greatly improve their utility for chemical synthesis. Toward this end, we analyzed the structures and selectivity of three halogenase variants evolved to halogenate tryptamine with orthogonal selectivity. Crystal structures and reversion mutations revealed key residues involved in altering halogenase selectivity. Density functional theory calculations and molecular dynamics simulations are both consistent with hypohalous acid as the active halogenating species in FDH catalysis. This model was used to accurately predict the site selectivity of halogenase variants toward different synthetic substrates, providing a valuable tool for implementing halogenases in biocatalysis efforts.

  PublisherOA PDFDOI

• Sebetralstat (KVD900): A Potent and Selective Small Molecule Plasma Kallikrein Inhibitor Featuring a Novel P1 Group as a Potential Oral On-Demand Treatment for Hereditary Angioedema

  Journal of Medicinal Chemistry · 2022-10-17 · 26 citations

  articleOpen access

  Hereditary angioedema (HAE) is a rare genetic disorder in which patients experience sudden onset of swelling in various locations of the body. HAE is associated with uncontrolled plasma kallikrein (PKa) enzyme activity and generation of the potent inflammatory mediator, bradykinin, resulting in episodic attacks of angioedema. Herein, we disclose the discovery and optimization of novel small molecule PKa inhibitors. Starting from molecules containing highly basic P1 groups, which typically bind to an aspartic acid residue (Asp189) in the serine protease S1 pocket, we identified novel P1 binding groups likely to have greater potential for oral-drug-like properties. The optimization of P4 and the central core together with the particularly favorable properties of 3-fluoro-4-methoxypyridine P1 led to the development of sebetralstat, a potent, selective, orally bioavailable PKa inhibitor in phase 3 for on-demand treatment of HAE attacks.

  PublisherOA PDFDOI

• Poly(dehydroalanine): Synthesis, Properties, and Functional Diversification of a Fluorescent Polypeptide

  Journal of the American Chemical Society · 2022-02-27 · 20 citations

  articleOpen access

  Via the design of a new, soluble poly(S-alkyl-l-cysteine) precursor, a route was developed for the successful preparation of long-chain poly(dehydroalanine), ADH, as well as the incorporation of dehydroalanine residues and ADH segments into copolypeptides. Based on experimental and computational data, ADH was found to adopt a previously unobserved “hybrid coil” structure, which combines the elements of 25-helical and 310-helical conformations. Analysis of the spectroscopic properties of ADH revealed that it possesses a strong inherent blue fluorescence, which may be amenable for use in imaging applications. ADH also contains reactive electrophilic groups that allowed its efficient modification to functionalized polypeptides after reactions under mild conditions with thiol and amine nucleophiles. The combined structural, spectroscopic, and reactivity properties of ADH make it a unique reactive and fluorescent polypeptide component for utilization in self-assembled biomaterials.

  PublisherOA PDFDOI

• Correction to “Catalase Involved in Oxidative Cyclization of the Tetracyclic Ergoline of Fungal Ergot Alkaloids”

  Journal of the American Chemical Society · 2022-05-26

  erratum

  ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to "Catalase Involved in Oxidative Cyclization of the Tetracyclic Ergoline of Fungal Ergot Alkaloids"Yongpeng YaoYongpeng YaoMore by Yongpeng Yao, Chunyan AnChunyan AnMore by Chunyan An, Declan EvansDeclan EvansMore by Declan Evans, Weiwei LiuWeiwei LiuMore by Weiwei Liu, Wei WangWei WangMore by Wei Wang, Guangzheng WeiGuangzheng WeiMore by Guangzheng Wei, Ning DingNing DingMore by Ning Ding, K. N. Houk*K. N. HoukMore by K. N. Houkhttps://orcid.org/0000-0002-8387-5261, and Shu-Shan Gao*Shu-Shan GaoMore by Shu-Shan Gaohttps://orcid.org/0000-0001-6335-2052Cite this: J. Am. Chem. Soc. 2022, 144, 22, 10094Publication Date (Web):May 26, 2022Publication History Published online26 May 2022Published inissue 8 June 2022https://pubs.acs.org/doi/10.1021/jacs.2c04520https://doi.org/10.1021/jacs.2c04520correctionACS PublicationsCopyright © 2022 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views897Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (476 KB) Get e-Alertsclose Get e-Alerts

  PublisherDOI

Frequent coauthors

• K. N. Houk

  University of California, Los Angeles

  10 shared

• L.W. Crim

  Memorial University of Newfoundland

  9 shared

• Gary R.W. Pitt

  Blackburn College

  5 shared

• Michael Szelke

  Chilworth Technology (United Kingdom)

  5 shared

• Doreen M. Ashworth

  Vantia (United Kingdom)

  5 shared

• Thomas Griesbacher

  4 shared

• Wei Wang

  Institute of Botany

  4 shared

• Guangzheng Wei

  Shanghai Jiao Tong University

  4 shared

Education

• Ph. D., Molecular Biology

  University of California, Los Angeles

  2023

• B.S., Mathematics

  Pennsylvania State University

  2017

• B.S., Biochemistry and Molecular Biology

  Pennsylvania State University

  2017

Awards & honors

• H.W. Magoun Distinguished Lectureship
• Samuel Eiduson Student Lectureship
• Arnold Scheibel Distinguished Fellow in Neuroscience Lecture
• Community Scholars Awards
• Eva Kavan Prize