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A Liquid-Phase Continuous-Flow Peptide Synthesizer for Preparing C-terminal Free Peptides
Natsumi Iwanaga, , Yokogawa Electric Corporation
Despite the importance of peptide drugs, their production has been usually performed by unsustainable and time-consuming methods. Conventional peptide production requires repeated amidation and deprotection steps that increase the amount of waste and the time and effort required. In this presentation, an automated continuous-flow liquid-phase peptide synthesizer for the preparation of C-terminal free peptides is presented. The synthesizer comprises an amidation unit with a micro-flow reactor, an extraction unit with mixer settlers, a concentration unit with a thin-layer evaporator, and a control unit. A crude dipeptide, Fmoc-Ala-Phe-OH, and a tripeptide, Fmoc-Ala-Phe-Phe-OH, that was directly obtained from the crude dipeptide, were synthesized using the system. The steadiness of the flow system was continuously monitored by measuring the process parameters, namely the flow rate, pressure and temperature. The peptide synthesis was monitored using a near-infrared (NIR) sensor. This system enabled the first liquid-phase continuous-flow peptide synthesis, including aqueous workup and concentration, and the in-line NIR monitoring of peptide-bond formation. It will contribute to enhancing efficiency in peptide production.
Development of a Flexible Open-Source Microfluidic System; Flow Chemistry and the Synthesis of PET-Tracer for Cancer Studies.
Florian Menzel, Ph.D. Student, University Tuebingen
We introduce a low-cost open-source flow system including a dual syringe pump, a pressure sensor, a back pressure regulator as well as custom 3D-printed flow reactors made of PEEK (polyether ether ketone).[1] Commercially available flow systems can be very expensive with equipment often exceeding 30,000 €.[2, 3] The system we present can be built for around €500 and contributes to increasing the usage of flow chemistry in research facilities. Particularly, due to the limited space in radiochemical facilities, commercially available flow systems and rarely used. A compact and customizable system is therefore advantageous, and 3D-printing technology provides the solution. As a proof of concept, we designed, developed, and tested a custom flow process for the synthesis of [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG), the most commonly used PET tracer.[4] The system is designed to perform the typical functions and operations involved in radiotracer preparation, i.e., radiofluorination, dilution, SPE trapping, deprotection, and SPE elution, reducing the overall radiation exposure for laboratory staff. With this proof-of-concept in hand, the system can be adapted to meet the requirements of many other syntheses.
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