Microwave peptide synthesizer

A recent development in this context is the Liberty system introduced by CEM in 2004 (see Fig. 3.25). This instrument is an automated microwave peptide synthesizer, equipped with special vessels, applicable for the unattended synthesis of up to 12 peptides employing 25 different amino acids. This tool offers the first commercially available dedicated reaction vessels for carrying out microwave-assisted solid-phase peptide synthesis. At the time of writing, no published work accomplished with this instrument was available. 

Automated peptide synthesizers have been in use for several decades and have provided much needed assistance for manual synthesis of long peptides. In 2003, CEM Corporation introduced the first automated microwave peptide synthesizer, Odyssey. This system was updated shortly afterwards to the current version, Liberty (Fig. 20.6). 

Peptoids containing up to 50 residues have been synthesized in reasonable yield using the submonomer approach [17]. Different instrumentations have been used for peptoid synthesis such as manual synthesis in syringes equipped with a fritted filter [21], automated peptide synthesizers [28], automated microwave peptide synthesizers [12], and parallel synthesizers [34]. 

Fig. 10 Liberty (CEM Corporation), the first automated microwave solid-phase peptide synthesizer, is shown on the left-, the available reaction vessel setup for solid-phase synthesis is depicted on the right...

The Liberty system is a sequential peptide synthesizer capable of complete automated synthesis, including cleavage, of up to twelve different peptides. The system uses the Discover single-mode microwave reactor that has been widely used in organic synthesis. 

CEM also offers a manual peptide synthesizer. Discover SPS (Fig. 20.7). This system is also based on the Discover microwave reactor. It uses a 25 mL polypropylene SPE cartridge that is held in place in the reactor. Fiber-optic temperature monitoring is included in the system and enables control of microwave power delivery. A vacuum manifold station is provided that enables rapid washing and filtration of reagents during the cycle. The system can be upgraded to the automated Liberty. 

Instruments Syro II peptide synthesizer (MultiSynTech GmbH, Germany now Biotage, Sweden), Biotage Initiator microwave instrument, and a solid-phase reaction vessel (Biotage AB, Uppsala, Sweden) [15],... 

As the interest in biopharmaceuticals and peptide science has increased over the last 20-30 years, new manufactures of peptide synthesizers have emerged. The increased competition on the marked and the need for better synthesizers have led to even more sophisticated instruments. The synthesizers of today can have many special features such as parallel synthesis capability, conductive or microwave heating, UV monitoring, ability for small- or large-scale synthesis, as well as the ability for TFA cleavage (Table 1). However, more options are not always better, especially if it comes with a risk of reduced robustness of operation. 

Automated Microwave-Assisted Solid-Phase Peptide Synthesizers... 

Equipment Fully automated X-Y robot using a single-mode microwave-assisted solid-phase peptide synthesizer (Syro Wave , Biotage AB). 

Equipment Single mode microwave synthesizer configured for manual peptide synthesis equipped with a fiber optic temperature probe (Discover SPS microwave-assisted peptide synthesizer, GEM Corporation) (rrr Note 1). 

Equipment Automated microwave-assisted peptide synthesizer (Liberty microwave-assisted peptide synthesizer, GEM Gorporation). 

The actual amount used by the automated microwave-assisted peptide synthesizer will be lower than the volumes listed. These volumes include a 10 % overage to ensure smooth operation of... 

Another approach to labeling OC with 18F was reported by Hostetler et al. [61]. OC was labeled via an in situ peptide coupling of 4-[18F]fluorobenzoic acid ([18F]FBA) with the N-terminus of OC to provide 4-[18F]fluorobenzoyl-OC ([18F]FB-OC).The process of synthesizing [18F]FB-OC involved a new efficient, one-pot synthesis of [18F]FBA using a microwave cavity and the combination of reagents,1,3-dicyclohexylcarbodiimide and l-hydroxy-7-azabenzo-triazole. Unfortunately, [18F]FB-OC also showed high liver uptake and low uptake in so-... 

Besides performing multiple syntheses in parallel, the accelerating of reaction rates may also achieve the same result— production of multiple peptides in the same time period. CEM (http //www.cem.com) has employed microwave irradiation to shorten both coupling and deprotection times. Their synthesizer, Odyssey (Fig. 7), achieves one cycle of peptide synthesis (Fmoc-based) in less than 10 min and is theoretically capable of the synthesis of 12 peptides in a row. However, for each new peptide the reaction vessel has to be cleaned and new batch of resin has to be transferred into it. This step raises concerns with the authors of this review about the possibility of cross-contamination. 

In 2002, a single mode microwave synthesizer was also shown to accelerate the coupling reaction of several 3mer peptides [41]. Temperatures of up to 120 °C were used for the coupling reaction. In 2003, microwave energy was applied to the complete Fmoc SPPS cycle, including both deprotection and coupling steps [42]. The... 

Erythropoietin (EPO) is a naturally occurring protein responsible for red blood cell production. A 20mer peptide mimic of this natural protein has been synthesized in 8 h by use of microwave SPPS. Purity was higher than that obtained in 5 days by conventionally synthesis [33] and the biological activity was reported to be equal to that of the conventionally synthesized material, as shown in Fig. 20.16. 

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