Synthesis of Cyclic Peptides in SPPS with Npb-OH Photolabile Protecting Group |
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| Authors: | Tingting Chen Gang Wang Lin Tang Hongpeng Yang Jing Xu Xiaoxue Wen Yunbo Sun Shuchen Liu Tao Peng Shouguo Zhang Lin Wang |
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| Institution: | Institute of Radiation Medicine, Beijing 100850, China; (T.C.); (L.T.); (H.Y.); (J.X.); (X.W.); (Y.S.); (S.L.) |
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| Abstract: | Significant efforts have been made in recent years to identify more environmentally benign and safe alternatives to side-chain protection and deprotection in solid-phase peptide synthesis (SPPS). Several protecting groups have been endorsed as suitable candidates, but finding a greener protecting group in SPPS has been challenging. Here, based on the 2-(o-nitrophenyl) propan-1-ol (Npp-OH) photolabile protecting group, a structural modification was carried out to synthesize a series of derivatives. Through experimental verification, we found that 3-(o-Nitrophenyl) butan-2-ol (Npb-OH) had a high photo-release rate, high tolerance to the key conditions of Fmoc-SPPS (20% piperidine DMF alkaline solution, and pure TFA acidic solution), and applicability as a carboxyl-protective group in aliphatic and aromatic carboxyl groups. Finally, Npb-OH was successfully applied to the synthesis of head–tail cyclic peptides and side-chain–tail cyclic peptides. Moreover, we found that Npb-OH could effectively resist diketopiperazines (DKP). The α-H of Npb-OH was found to be necessary for its photosensitivity in comparison to 3-(o-Nitrophenyl)but-3-en-2-ol (Npbe-OH) during photolysis-rate verification. |
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| Keywords: | photolabile protecting groups Npb-OH cyclic peptides |
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