NOF Corporation is a chemical company that handles various chemical products, including functional chemicals, pharmaceuticals, and medical products. Within the peptide field, NOF Corporation provides polydisperse and monodisperse PEGs with functional groups for protein and peptide conjugates.
Peptide therapy has advantages such as high specificity and good efficacy but faces challenges like low stability and short half-life. Satoshi Kishida, a Research Scientist at NOF Corporation introduced techniques such as cyclization, manipulation of amino acid sequences, and polymer conjugation (PEGylation) to address these drawbacks. Kishida explained that PEGylation was the most effective of all the methods due to its ability to improve stability and half-life.
Yet, PEGylated peptides have decreased bioactivity and the presence of a PEG chain presents difficulties regarding a peptide’s interaction with a receptor. Therefore, NOF corporation developed its PEG SUNBRIGHT BD series, a technology that aimed to retain half-life while improving bioactivity. This class of PEGs consists of a PEG chain for retaining half-life, a hydrolysable acetal linker for releasing the peptide, and a functional group to link the peptide.
Studies showed that the linker is critical for maintaining the half-life and gradually releases the native peptide under physiological conditions. The peptide release occurs via hydrolysis and subsequent elimination, independent of enzymatic activity. Kishida added that the release rates can be tweaked by modifying the aromatic moiety in the acetal linker.
In vitro studies with insulin conjugates with releasable PEGs at 37 degrees showed a gradual release of peptides. The team also experimented with various aromatic structures to control the release rate. According to Kishida: “In cell proliferation assays, releasable PEGylated IL-2 showed improved bioactivity compared to non-releasable PEGylated IL-2.” The in vivo studies with the insulin conjugates showed an improved PK profile and therapeutic efficacy among releasable PEGs compared with non-releasable PEGylated insulin.
In summary, releasable PEG conjugates address key challenges in peptide therapy, improving stability, half-life, and bioactivity without significant toxicity. The technology accommodates customisable release rates for optimised therapeutic outcomes.
