Corrin Ring Modification in Peptide Drug Development – a Brief History of “Corrination”

Abstract

Recently, the term “corrination” was coined to describe the conjugate modification of a peptide, protein, small molecule, or radionuclide with a corrin ring-containing molecule. By exploiting the innate chemicophysical properties of corrin ring-containing compounds, 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. In this mini review, the design and synthetic approaches to peptide corrination are described, along with examples of in vitro, ex vivo, and in vivo biological evaluations of corrinated conjugates, which demonstrate the broad applicability of the technique, namely 1) mitigated peptide aggregation, 2) improved protection against proteolysis, 3) reduced negative side effects via targeted localization, 4) regioselective production of peptide disulfide bonds, and 5) improved oral drug absorption. Herein, it is described 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.