Monodispersed PEG linkers are pure compounds with a single molecular weight. In contrast, polyPEG linkers contain variations in molecular weight with an average molecular weight. The use of polyPEG linkers in drug development has led to problems in biological applications due to steric hindrance and binding.1
With advancements in both synthetic and purification chemistry over the past two decades, monodispersed PEG linkers have become more commercially viable. Monodispersed PEG linkers have been found to be beneficial in drug design, specifically in small molecule drugs. Some of the problems that are often seen in small molecule drugs include its ability to be easily removed from the body, low solubility and less target-specificity.2 The introduction of monodispersed PEG linkers to small molecule drugs increases the drug’s solubility and molecular weight. This may allow an extended drug half-life in the body.3 The use of monodispersed PEG linkers has also improved drug development with its ability to produce homogeneous PEGylated drugs with a specific molecular weight.
Figure 1: Chemical structure of Movantik. Movantik is used for to reduce the occurrence of OIC and OBD upon the consumption of opioids for pain management.Pharmaceutical companies such as NEKTAR and AstraZeneca have made use of attached PEG linkers to small molecule drugs. OBD and OIC medications such as Movantik (naloxol) incorporate monodispersed PEG linkers to enhance the efficacy of the drug. Movantik includes an m-PEG7 linker. The introduction of this linker to Movantik reduced transport across the blood-brain barrier preventing side-effects to the central nervous system.
Reference
1 Povoski, Stephen P et al. “Single Molecular Weight Discrete PEG Compounds: Emerging Roles in Molecular Diagnostics, Imaging and Therapeutics.” Expert review of molecular diagnostics 13.4 (2013): 315–319. PMC. Web. 6 July 2018.
2 Pasut, Gianfranco, Veronese, Francesco M., Drug Discovery 10, 21 (2005).
3 Swierczewska, Magdalena, Kang Choon Lee, and Seulki Lee. “What Is the Future of PEGylated Therapies?” Expert opinion on emerging drugs 20.4 (2015): 531–536. PMC. Web. 6 July 2018.
