Kang Choon Lee
SungKyunKwan University, South Korea
Title: Strategic PEGylation: Half-life extension of biologic drugs
Biography
Biography: Kang Choon Lee
Abstract
The tremendous potential of biologic drugs is hampered by short half-lives in vivo, resulting in significantly lower potency than activity seen in vitro. These short-acting therapeutic agents require frequent dosing profiles that can reduce applicability to the clinic, particularly for chronic conditions. Therefore, half-life extension technologies are entering the clinic to enable improved or new biologic therapies. PEGylation is a commonly utilized technique to improve drug solubility and stability, prolong blood circulation time, reduce immunogenicity, and decrease dosing frequency. As with any form of molecular modification, the active site is affected and can drastically decrease the bioactivity of the therapeutic agent, especially when the modification is performed on a small molecular weight molecule like peptides and small proteins. Steric hindrance from high molecular weight PEG can lead to a dramatic loss in the biological and pharmacological activity of the molecules. The higher the molecular weight, the lower the bioactivity. Therefore, it is generally accepted that a balance must be struck between the molecular weight of the PEG and the activity of the therapeutic molecule to reach sufficient drug efficacy. The strategic PEGylation technique introduced here offers many benefits over the conventional PEGylated forms of peptides and proteins. Strategic PEGylation signifies that a tradeoff of PEGylation for bioactivity is not necessary. Specifically, this abstract focuses on the strategic PEGylation of potent therapeutic peptides for GLP-1 analogues as a model peptide. Strategic PEGylation can be a platform technology to extend the half-life while preserving the biological activity of peptide and small protein drugs.
