dc.contributor.author | Immel, Jacob R. | |
dc.contributor.author | Chilamari, Maheshwerreddy | |
dc.contributor.author | Bloom, Steven | |
dc.date.accessioned | 2021-12-06T21:46:23Z | |
dc.date.available | 2021-12-06T21:46:23Z | |
dc.date.issued | 2021-06-30 | |
dc.identifier.citation | Immel, J. R., Chilamari, M., & Bloom, S. (2021). Combining flavin photocatalysis with parallel synthesis: a general platform to optimize peptides with non-proteinogenic amino acids. Chemical science, 12(29), 10083–10091. https://doi.org/10.1039/d1sc02562g | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/32259 | |
dc.description.abstract | Most peptide drugs contain non-proteinogenic amino acids (NPAAs), born out through extensive structure–activity relationship (SAR) studies using solid-phase peptide synthesis (SPPS). Synthetically laborious and expensive to manufacture, NPAAs also can have poor coupling efficiencies allowing only a small fraction to be sampled by conventional SPPS. To gain general access to NPAA-containing peptides, we developed a first-generation platform that merges contemporary flavin photocatalysis with parallel synthesis to simultaneously make, purify, quantify, and even test up to 96 single-NPAA peptide variants via the unique combination of boronic acids and a dehydroalanine residue in a peptide. We showcase the power of our newly minted platform to introduce NPAAs of diverse chemotypes-aliphatic, aromatic, heteroaromatic-directly into peptides, including 15 entirely new residues, and to evolve a simple proteinogenic peptide into an unnatural inhibitor of thrombin by non-classical peptide SAR. | en_US |
dc.publisher | Royal Society of Chemistry | en_US |
dc.rights | © 2021 The Author(s). Published by the Royal Society of Chemistry. This work is licensed under a Creative Commons Attribution 4.0 International License. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.title | Combining flavin photocatalysis with parallel synthesis: a general platform to optimize peptides with non-proteinogenic amino acids | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Immel, Jacob R. | |
kusw.kuauthor | Chilamari, Maheshwerreddy | |
kusw.kuauthor | Bloom, Steven | |
kusw.kudepartment | Medicinal Chemistry | en_US |
dc.identifier.doi | 10.1039/d1sc02562g | en_US |
dc.identifier.orcid | https://orcid.org/ 0000-0002-4205-4459 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC8317666 | en_US |
dc.rights.accessrights | openAccess | en_US |