Microwave-assisted solid-phase synthesis of side-chain to side-chain lactam-bridge cyclic peptides

• Published in: Bioorganic & medicinal chemistry letters Vol. 25; no. 24; pp. 5708 - 5711
• Main Authors: Tala, Srinivasa R., Schnell, Sathya M., Haskell-Luevano, Carrie
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-12-2015
• Subjects: alpha-MSH - analogs & derivatives; alpha-MSH - chemical synthesis; alpha-MSH - chemistry; alpha-MSH - metabolism; Animals; Cyclic peptides; Lactam-bridge cyclic peptides; Lactams - chemistry; Melanocyte-Stimulating Hormones - chemical synthesis; Melanocyte-Stimulating Hormones - chemistry; Melanocyte-Stimulating Hormones - metabolism; Mice; Microwave assisted synthesis; Microwaves; MTII; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - chemistry; Protein Binding; Receptors, Melanocortin - antagonists & inhibitors; Receptors, Melanocortin - metabolism; SHU9119; Solid-Phase Synthesis Techniques; DIEA; MTII; TES; H2O; Cyclic peptides; PyBOP; SHU9119; MBHA; TFA; DCM; RP-HPLC; NMP; MWA-SPPS; HOBt; Lactam-bridge cyclic peptides; HBTU; Microwave assisted synthesis; NDP; HATU; DMF; MCR; TIS
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.10.095

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Side-chain to side-chain lactam-bridged cyclic peptides have been utilized as therapeutic agents and biochemical tools. Previous synthetic methods of these peptides need special reaction conditions, form side products and take longer reaction times. Herein, an efficient microwave-assisted synthesis of side-chain to side-chain lactam-bridge cyclic peptides SHU9119 and MTII is reported. The synthesis time and efforts are significantly reduced in the present method, without side product formation. The analytical and pharmacological data of the synthesized cyclic peptides are in accordance with the commercially obtained compounds. This new method could be used to synthesize other side-chain to side-chain lactam-bridge peptides and amenable to automation and extensive SAR compound derivatization.