{"title":"Corrin Ring Conjugation in Peptide Drug Development - A Brief History of 'Corrination'.","authors":"Robert P Doyle, Nancy Cham","doi":"10.1002/cmdc.202500129","DOIUrl":null,"url":null,"abstract":"<p><p>Recently, we coined the term 'corrination' to describe the conjugate modification of a peptide, protein, small molecule, or radionuclide with a corrin ring-containing molecule. By exploiting the innate chemico-physical properties of corrin ring-containing compounds, both in general and specifically via the innate dietary B12 uptake pathway in mammals, corrination has been explored for drug development and targeted/localized delivery of probes and therapeutics. Most recently, it is in the field of peptide-based therapeutics that corrination is generating significant interest. Peptide-based drugs possess several limitations that restrict their clinical application, including poor solubility and stability, low oral bioavailability, and negative side effects often due to drug distribution. Therefore, methods must be developed to address these issues without affecting the peptide's functionality. In this review, we describe the design and synthetic approaches to peptide corrination, along with examples, which demonstrate the broad applicability of the technique, namely 1) mitigated peptide aggregation, 2) improved protection against proteolysis, 3) reduced side effects via targeted localization 4) regioselective production of peptide disulfide bonds, 5) improved oral drug absorption. We describe how corrination offers a facile route to improving peptide pharmacokinetic and pharmacodynamic properties, making this a useful platform technology in the field of peptide drug development.</p>","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500129"},"PeriodicalIF":3.6000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ChemMedChem","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/cmdc.202500129","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Recently, we coined the term 'corrination' to describe the conjugate modification of a peptide, protein, small molecule, or radionuclide with a corrin ring-containing molecule. By exploiting the innate chemico-physical properties of corrin ring-containing compounds, both in general and specifically via the innate dietary B12 uptake pathway in mammals, corrination has been explored for drug development and targeted/localized delivery of probes and therapeutics. Most recently, it is in the field of peptide-based therapeutics that corrination is generating significant interest. Peptide-based drugs possess several limitations that restrict their clinical application, including poor solubility and stability, low oral bioavailability, and negative side effects often due to drug distribution. Therefore, methods must be developed to address these issues without affecting the peptide's functionality. In this review, we describe the design and synthetic approaches to peptide corrination, along with examples, which demonstrate the broad applicability of the technique, namely 1) mitigated peptide aggregation, 2) improved protection against proteolysis, 3) reduced side effects via targeted localization 4) regioselective production of peptide disulfide bonds, 5) improved oral drug absorption. We describe how corrination offers a facile route to improving peptide pharmacokinetic and pharmacodynamic properties, making this a useful platform technology in the field of peptide drug development.
期刊介绍:
Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies.
ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs.
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