Mr. Keiichi Masuya is Chief Operating Officer at PeptiDream. He explains: “Our company was established as a spin-off project from the research carried out by Professor Hiroaki Suga, who at that time served as a professor at the Research Center for Advanced Science and Technology, the University of Tokyo. Our business was founded on the mission to contribute to drug discovery using Peptide Discovery Platform System (PDPS), a technology that was developed to generate non-standard peptides by Professor Suga, which is based on his Flexizyme technology."
"Our company name PeptiDream may imply that we specialize in peptides. However, we only start with peptides and then apply them to a variety of fields. In addition to drug discovery with peptides, we have developed peptides with reduced molecular weights to serve as tools for applications in fields other than drug discovery, such as agrochemicals. Our goal is to apply this excellent technology platform in various forms. The biology department, called Discovery, which serves as our company’s technology foundation, screens for and selects candidate peptides that could successfully bind to proteins. Then, the chemists in the R&D department actually synthesize the selected peptides to support this technology.”
Nishimaru fills in: “At the time of establishment, PeptiDream was located on the same site as the Suga laboratory, and therefore borrowed the Syro I system from their laboratory for all synthesis activities. After the Suga laboratory moved to Hongo, PeptiDream needed its own synthesis system; thus, we decided to purchase our own Syro I.”
Nishimaru recalls: “I remember that we did consider other candidates, but ultimately decided to go with Syro I because we were most familiar with it. From the standpoint of effeciency, ease of use was also an important factor.”
Nishimaru continues: “The first automated peptide synthesizer that I used was the Syro I system borrowed from the Suga laboratory. I remember that it was intuitive, or perhaps I should say, it was very easy to use. In particular, the combinations of settings were simple. Therefore, I have used Syro I from then until now. The greatest advantage of Syro I is its capability for automated parallel synthesis. Our department needs to synthesize peptides with various sequences, as well as peptides with the same sequence but under slightly varying reaction conditions. Syro I is a very convenient system to use for the synthesis of a wide variety of peptides, in contrast to manual synthesis or one-by-one synthesis, which is too time-consuming.”
“We began using Initiator+ Alstra around the start of the fiscal year of 2013, about two years after the introduction of Syro I”, Nishimaru recalls. “At that time, we considered using microwave-assisted synthesis and were given a demonstration of the Biotage semi-automated peptide synthesizer Initiator+ SP Wave. We did appreciate the potential effects of microwave-assisted synthesis, but considered that full automation was still preferable and therefore dithered. In the meantime, the fully automated synthesizer Initiator+ Alstra became commercially available. We preferred this system and thus introduced it. It was actually very easy to use, and we now have three Initiator+ Alstra systems.”
“That’s right” Nishimaru confirms. “Since we now have more clients, more samples, and more peptides to be synthesized, we require improved efficiency of synthesis, which is possible with Initatior+Alstra.”
“It's a Godsend!” Fukuda exclaims.
Tanaka explains: “With the aid of a microwave, Initiator+ Alstra allows for the clean synthesis of non-naturally-occurring sequences that would be less likely to be coupled at room temperature. We had not previously carried out microwave-assisted synthesis before the introduction of Initiator+ Alstra and had been concerned that microwaves might destroy or damage the products. Surprisingly, quite clean syntheses can actually be achieved with this approach. The actual synthesis temperature is about 75 °C, which never leads to the destruction of products. With the microwave, we have succeeded in clean synthesis of peptides using amino acids that could not be coupled at room temperature.”
Fukuda comments: “As Initiator+ Alstra was my first use of microwave-assisted peptide synthesis, I was also initially unsure about whether or not it would be acceptable. It was not until I actually used it for synthesis activities that I realized how useful the microwave was and understood that in some cases, synthesis would only be possible using microwaves.”
Fukuda continues: “When I was conducting manual synthesis at my previous job, coupling of one residue took about one hour. In contrast, at PeptiDream, coupling of one residue takes only seven minutes with the use of Initiator+ Alstra. This was a shocking change.”
Tanaka fills in: “The increased rate enables the synthesis of a greater variety of peptides.”
Fukuda agrees: “That’s right. Indeed, the synthesis of a wide variety of peptides is needed.”
Tanaka elaborates: “In that regard, efficient synthesis is very important. Therefore, full automation is a very convenient and indispensable function. If we program the Initiator+ Alstra system before going home at the end of the work day, the system will synthesize the peptides overnight, and they will be available the next morning. This allows us to synthesize more peptides in a day, which is very helpful.”
Fukuda confirms: “This system allows us to make effective use of the nighttime.”
Nishimaru: “The software of Initiator+ Alstra is more intuitive to use compared to that of Syro I, although the latter is also still good. However, the software of Initiator+ Alstra is more flexible.”
Fukuda: “A big advantage is that we can interrupt the operation to make changes as necessary. When using other systems, in order to stop the operation, we have to wait until the operation has reached a certain stage of progress. In that regard, Initiator+ Alstra allows us to make relatively small changes as we go along, which is a very practical feature.”
Tanaka: “Initiator+ Alstra is very easy to use because it can be easily applied to different circumstances; for example, by adding reagents that were manually activated. Because of the large number of peptides that need to be synthesized, all three Initiator+ Alstra systems are always running simultaneously.”
“How do you use Syro I and Initiator+ Alstra separately?”
Nishimaru: “It depends on the differences in sequences. First, we review the sequences presented by the Discovery Group, and then select Syro I for those that are considered to be relatively easy to synthesize. For those that appear to be difficult to synthesize at room temperature, we are most likely to choose Initiator+ Alstra. We would not be able to do our work on time without synthesizing in parallel because we now have many things to be synthesized.” (Laughs)
Nishimaru: “We use dimethyl sulfoxide (DMSO) for the purpose of peptide synthesis. As you know, DMSO is a solvent that is very difficult to evaporate. We considered using reaction conditions without DMSO, but, as expected, many of the reactions could not occur under this condition. However, we heard about the V-10 system, that was capable of evaporating DMSO and therefore introduced it.”
Tanaka: “We were very surprised because we had no idea that evaporation of DMSO was feasible.”
Nishimaru: “We use Isolera for purifying the peptide building blocks. This software is also easy to use and is convenient.”
Masuya: “We intend to further expand our field of activities. As explained earlier, we will be fully engaged in applying PeptiDream’s excellent technology to various fields. Thus far, we have diversified into applications in the agrochemical, food, and cosmetic industries, as well as with pharmaceuticals. We may need more and more synthesizers accordingly. At this point, we may actually become the company that uses the most Biotage peptide products in the world!” (Laughs).
Stated capital: 2,743 million
Head office: Tokyo
PeptiDream Inc. was founded in July 2006 by Professor Hiroaki Suga, Graduate School of Science, the University of Tokyo. PeptiDream carries out research and development of drug candidates using the Peptide Discovery Platform System (PDPS), its proprietary platform system for drug discovery and development that was developed based on the Flexizyme (artificial ribozyme) technology developed by Prof. Suga. PeptiDream is a leading peptide drug company that aims at helping patients around the world through the discovery and development of innovative drugs to meet various medical needs. PeptiDream was listed on the Mothers in June 2013 and has now further expanded its field of activities.
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