Liquid Phase Peptide Synthesis via One‐Pot Nanostar Sieving (PEPSTAR)
| Autor: | Andrew G. Livingston, Jet Yeo, Seoyeon Chung, Carla V. Luciani, Sergey V. Tsukanov, Michael E. Kopach, Ludmila G. Peeva, Piers R. J. Gaffney, Fernando Albericio, Daeok Kim, Kevin D. Seibert |
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| Přispěvatelé: | Eli Lilly & Company (USA) |
| Rok vydání: | 2021 |
| Předmět: |
Chemistry
Multidisciplinary liquid phase peptide synthesis Dispersity Peptide 010402 general chemistry 01 natural sciences Catalysis chemistry.chemical_compound Solid-phase synthesis organic solvent nanofiltration (OSN) Phase (matter) Amide Peptide synthesis Peptide Synthesis Research Articles chemistry.chemical_classification Octreotate Science & Technology 010405 organic chemistry Organic Chemistry General Medicine General Chemistry Combinatorial chemistry 0104 chemical sciences Chemistry chemistry membranes Physical Sciences peptides Nanofiltration 03 Chemical Sciences Research Article |
| Zdroj: | Angewandte Chemie (International Ed. in English) |
| ISSN: | 1521-3773 1433-7851 |
| Popis: | Herein, a one‐pot liquid phase peptide synthesis featuring iterative addition of amino acids to a “nanostar” support, with organic solvent nanofiltration (OSN) for isolation of the growing peptide after each synthesis cycle is reported. A cycle consists of coupling, Fmoc removal, then sieving out of the reaction by‐products via nanofiltration in a reactor‐separator, or synthesizer apparatus where no phase or material transfers are required between cycles. The three‐armed and monodisperse nanostar facilitates both efficient nanofiltration and real‐time reaction monitoring of each process cycle. This enabled the synthesis of peptides more efficiently while retaining the full benefits of liquid phase synthesis. PEPSTAR was validated initially with the synthesis of enkephalin‐like model penta‐ and decapeptides, then octreotate amide and finally octreotate. The crude purities compared favorably to vendor produced samples from solid phase synthesis. PEPSTAR, a “rising star” in peptide synthesis, features a “nanostar” support to grow peptides with organic solvent nanofiltration for isolation. The three‐armed and monodisperse nanostar enables efficient nanofiltration and real‐time reaction monitoring. A cycle consists of coupling, Fmoc removal and nanofiltration, which all performed continuously in a synthesizer to produce high purity peptide crudes through a one‐pot approach. |
| Databáze: | OpenAIRE |
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