Document Type
Article
Publication Date
6-23-2017
Abstract
CN2097 (R7Cs-sCYK[KTE(β-Ala)]V) is a rationally designed peptidomimetic that shows effectiveness in preclinical models for the treatment of neurological disorders, such as Angelman syndrome, traumatic brain injury (TBI), and stroke. Because of its potential therapeutic activity for the treatment of human CNS disorders, there was an urgent need to develop an efficient strategy for large-scale synthesis of CN2097. The synthesis of CN2097 was accomplished using Fmoc/tBu solid phase chemistry in multiple steps. Two different peptide fragments (activated polyarginine peptide Npys-sCR7 and CYK[KTE(β-Ala)]V) were synthesized, followed by solution phase coupling in water. Activation of the polyarginine (CR7) was achieved in situ during cleavage of protected peptide (C(Trt)R(Pbf)7) from the Rink amide resin using 5 equiv. of 2,2-dithopyridine in TFA:TIS:H2O (95:2.5:2.5, v/v/v) for 4 h. The disulfide coupling was efficient which provided a 60% yield.
Recommended Citation
Darwish S, Parang K, Marshall J, Goebel DJ, & Tiwari R. Efficient synthesis of CN2097 using in situ activation of sulfhydryl group. Tetrahedron Lett. 2017;31(2):3053-3056. doi: 10.1016/j.tetlet.2017.06.066
Copyright
Elsevier
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Medical Neurobiology Commons, Medicinal and Pharmaceutical Chemistry Commons, Neurology Commons, Other Pharmacy and Pharmaceutical Sciences Commons, Pharmaceutics and Drug Design Commons, Therapeutics Commons
Comments
NOTICE: this is the author’s version of a work that was accepted for publication in Tetrahedron Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Tetrahedron Letters, volume 31, issue 2, in 2017. DOI:10.1016/j.tetlet.2017.06.066
The Creative Commons license below applies only to this version of the article.