From small to large scale: optimizing and upscaling the synthesis of melanotan II (MT-II) - Melanocortin ReceptorAgonist, on PurePep® Chorus and PurePep® Sonata®+
Luísa Aguiar, Colton Quick, Juan Bello, Victor Nikolaev, Scott Harlow and Łukasz Frankiewicz
Gyros Protein Technologies, 4675 South Coach Drive, Tucson, Arizona, 85714, U.S.A.
α-Melanocyte Stimulating Hormone (α-MSH) is responsible for triggering the production of melatonin – body’s natural protection against ultraviolet (UV) radiation. α-MSH production is prompted, in itself, by the exposure of the skin to UV rays; however, stimulating the biosynthesis of melatonin prior to UV exposure could possibly prevent UV-induced skin cancer. Considering that the native form of α-MSH was too unstable in vivo to be administered as a therapeutic agent, a wide range of analogues were synthesized; [2-4] one of them is MT-II (Figure 1), a cyclic pseudopeptide with high resistance to enzymatic degradation and an extraordinary potency.Given the relevance of MT-II and the need for its production at a larger scale, our work focused on the optimization of a fully automated synthetic pathway, i.e., synthesis of the linear sequence and on-resin lactamization of the final peptide. In this work, we report the fully automated synthesis of MT-II on PurePep® Chorus using different coupling conditions and orthogonal protection schemes, for different cyclization strategies. Furthermore, we describe the upscale of MT-II synthesis, using the new PurePep® Sonata®+ large scale peptide synthesizer.