Theranostics 2016; 6(2):243-253. doi:10.7150/thno.14322
Chemical Conjugation of Evans Blue Derivative: A Strategy to Develop Long-Acting Therapeutics through Albumin Binding
1. Department of Nuclear Medicine, Xiamen Cancer Center, the First Affiliated Hospital of Xiamen University, Xiamen, China
2. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA
3. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361005, China
The efficacy of therapeutic drugs is highly dependent on their optimal in vivo pharmacokinetics. Albumin conjugation is considered to be one of the most effective means of protracting the short lifespan of peptides and proteins. In this study, we proposed a novel platform for developing long lasting therapeutics by conjugating a small molecular albumin binding moiety, truncated Evans blue, to either peptides or proteins. Using the anti-diabetic peptide drug Exendin-4 as a model peptide, we synthesized a new long-acting Exendin-4 derivative (denoted as Abextide). Through complexation with albumin in situ, the biological half-life of Abextide was significantly extended. The hypoglycemic effect of Abextide was also improved remarkably over Exendin-4. Thus, Abextide has considerable potential to treat type 2 diabetes. This strategy as a general technology platform can be applied to other small molecules and biologics for the development of long-acting therapeutic drugs.
Keywords: Exendin-4, Evans blue, Albumin-binding, PET, Abextide
Chen H, Wang G, Lang L, Jacobson O, Kiesewetter DO, Liu Y, Ma Y, Zhang X, Wu H, Zhu L, Niu G, Chen X. Chemical Conjugation of Evans Blue Derivative: A Strategy to Develop Long-Acting Therapeutics through Albumin Binding. Theranostics 2016; 6(2):243-253. doi:10.7150/thno.14322. Available from http://www.thno.org/v06p0243.htm