title: Chemical Conjugation of Evans Blue Derivative: A Strategy to Develop Long-Acting Therapeutics through Albumin Binding.
abstract: 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.
authors.affiliation: 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.
authors.forename: Haojun
authors.initials: H
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Guohao
authors.initials: G
authors.lastname: Wang
authors.affiliation: 2. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Lixin
authors.initials: L
authors.lastname: Lang
authors.affiliation: 2. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Orit
authors.initials: O
authors.lastname: Jacobson
authors.affiliation: 2. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.affiliation: 2. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 2. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: 2. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1. Department of Nuclear Medicine, Xiamen Cancer Center, the First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: 2. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.affiliation: 2. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000418:Albumins / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes / Q000737:chemistry; D005070:Evans Blue / Q000031:analogs & derivatives*; D000077270:Exenatide; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D014688:Venoms / Q000737:chemistry
chemical_list: D000418:Albumins; D003301:Copper Radioisotopes; D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D007004:Hypoglycemic Agents; D010455:Peptides; D019275:Radiopharmaceuticals; D014688:Venoms; D005070:Evans Blue; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D000077270:Exenatide
keywords: Abextide; Albumin-binding; Evans blue; Exendin-4; PET