Incorporation of aliphatic proline residues into recombinantly produced insulin

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dc.contributor.authorBreunig, Stephanie L.
dc.contributor.authorQuijano, Janine C.
dc.contributor.authorDonohue, Cecile
dc.contributor.authorHenrickson, Amy
dc.contributor.authorDemeler, Borries
dc.contributor.authorKu, Hsun Teresa
dc.contributor.authorTirrell, David A.
dc.date.accessioned2024-08-15T22:32:00Z
dc.date.available2024-08-15T22:32:00Z
dc.date.issued2023
dc.descriptionOpen access article. Creative Commons Attribution 4.0 International license (CC BY 4.0) applies
dc.description.abstractAnalogs of proline can be used to expand the chemical space about the residue while maintaining its uniquely restricted conformational space. Here, we demonstrate the incorporation of 4R-methylproline, 4S-methylproline, and 4-methyleneproline into recombinant insulin expressed in Escherichia coli. These modified proline residues, introduced at position B28, change the biophysical properties of insulin: Incorporation of 4-methyleneproline at B28 accelerates fibril formation, while 4-methylation speeds dissociation from the pharmaceutically formulated hexamer. This work expands the scope of proline analogs amenable to incorporation into recombinant proteins and demonstrates how noncanonical amino acid mutagenesis can be used to engineer the therapeutically relevant properties of protein drugs.
dc.description.peer-reviewYes
dc.identifier.citationBreunig, S. L., Quijano, J. C., Donohue, C., Henrickson, A., Demeler, B., Ku, H. T., & Tirrell, D. A. (2023). Incorporation of aliphatic proline residues into recombinantly produced insulin. ACS Chemical Biology, 18(12), 2574-2581. https://doi.org/10.1021/acschembio.3c00561
dc.identifier.urihttps://hdl.handle.net/10133/6859
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.publisher.departmentDepartment of Chemistry and Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.institutionCalifornia Institute of Technology
dc.publisher.institutionBeckman Institute City of Hope
dc.publisher.institutionUniversity of Lethbridge
dc.publisher.urlhttps://doi.org/10.1021/acschembio.3c00561
dc.subjectDissociation
dc.subjectGenetics
dc.subjectMonomers
dc.subjectNanofibers
dc.subjectPeptides and proteins
dc.subjectProlines
dc.subjectRecombinant proteins
dc.subjectInsulin
dc.titleIncorporation of aliphatic proline residues into recombinantly produced insulin
dc.typeArticle
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