Solid phase synthesis instruments-Automated

Synthesis on solid supports was first developed by Merrifield [1] for the assembly of peptides. It has expanded to include many different applications including oligonucleotide, carbohydrate, and small-molecule assembly (see Chapters 11 and 14). The repetitive cycle of steps involved in the solid-phase synthesis of biopolymers can be performed manually using simple laboratory equipment or fully automated with sophisticated instrumentation. This chapter examines typical solid-phase reaction kinetics to identify factors that can improve the efficiency of both manual and automated synthesis. The hardware and software features of automated solid-phase instruments are also discussed. The focus of this discussion is not on particular commercial model synthesizers but on the basic principles of instrument operation. These considerations can assist in the design, purchase, or use of automated equipment for solid-phase synthesis. Most contrasting features have advantages and disadvantages and the proper choice of instrumentation depends on the synthetic needs of the user. 

As the field of solid phase synthesis evolved, manufacturers designed systems based on the synergy between chemistry and engineering. A key component to an instrument is the handling of amino acids and their subsequent activation to couple to a polymeric support. The goal of an automated system is to duplicate conditions that provide stability to reactive species that might... 

Because of the inherent ability of solid-phase synthesis to be integrated and automated, numerous instruments were built from the onset of solid-phase chemistry, and this development culminated after the introduction of combinatorial chemistry methods. Operational simplicity of solid-phase synthesis contributed to the development of multiple solid-phase synthesis, where numerous reaction vessels are handled at the same time. In 1989, Schnorrenberg and Gerhardt" introduced the automated multiple synthesis of peptides in parallel fashion. Multiple synthesis in a continuous flow manner was also later reported. 

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. 

The repetitive nature of oligomeric synthesis has enabled the rapid implementation of solid-phase and automated methods for DNA [20,21,85,86] and peptide combinatorial libraries. Using these systems for the synthesis of single compounds or mixtures of compounds, multiple reaction vessels numbering 8 [45], 15 [80], 20 [59], 24 [50], 25 [57,58], 36 [53-55,77-79], 48 [26,39-41], or 96 [42-44] can be manipulated. Only a few of these systems enable automated resin mixing and splitting within the instrument to generate mixtures of compounds [53,59,78,87,88],... 

While chemical synthesis is mostly an art, with specialized reactions for both inorganic and inorganic synthesis, the complexities of biochemistry have nurtured specialized instruments that can split or assemble biomolecules. An automated solid-phase peptide synthesizer was introduced by Merrifield15 in 1963 this allows for the facile synthesis of oligopeptides (up to 100 amino acid units) [2], The enzyme DNA polymerase I was discovered by Komberg16 in 1957 this allowed the assembly of DNA from fragments [3]. 

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