Manual synthesizers

The replacement of some substances in the human body by manually synthesized materials is an important field of investigation in both medical and material sciences. 

Merck Temperature Controller Manual Synthesizer, then evolved into the Quest 210 by Argonaut Technologies, Inc., 887 Industrial Road, Suite G, San Carlos, CA 94070, US. 

Solid Phase Synthesis of a Chimeric Peptide With Boc Strategy The peptide was manually synthesized on MBHA resin (1.1 mmol/g capacity). 

Key Words Automation parallel synthesis solid phase synthesis manual synthesizer centrifugation review. 

This chapter provides a manual for a laboratory-hased short course to introduce the common techniques of solid-phase peptide synthesis (SPPS). The course provides students the opportunity to design and manually synthesize analogs of glutathione using relatively simple equipment available in any unsophisticated laboratory. The manual provides compact protocols for both the different steps of SPPS and the final cleavage of peptides from resin supports. We also introduce a simple method for the synthesis of combinatorial libraries of glutathione analogs that is suitable for those relatively unfamiliar with the field of peptide chemistry. 

Figure 1. Manually synthesized sequence derived from an epidermal growth factor-like domain in blood coagulation factor X. The numbers in the parentheses show the sequence position relative to the C-terminal. The arrow indicates the location of aspartimide formation and subsequent ring opening by piperidine to form an adduct.

Efficient parallel synthesis of larger numbers of single defined compounds plays an ever more important role in dmg research. While it is possible to manually synthesize mixtures of large numbers of compounds on a solid phase employing the spHt-and-mix method, in parallel single compound synthesis a number of reaction vessels equal to the number of desired final products has to be handled (at least in the final step of the synthetic sequence) [l]. This latter approach clearly benefits from, or even requires assistance of some sort of robotic equipment/ devices. 

The differentiation between a combination of one of these reaction blocks and a magnetic stirplate and a manual synthesizer is largely arbitrary. Versatile manual synthesizers (Table 3) that can be used for both solution- and solid-phase synthesis range from the aapptec Labmate to the Biichi Syncore, Chemspeed MSW 500, and Heidolph Synthesis 1 (Fig. 5). The Biichi Syncore can be equipped with a concentrator cover, which converts it into a parallel evaporator, or -with a filtration unit that permits top filtration from the reaction mixture and collection of the filtrate (Fig. 5). 

Fig. 5 Manual synthesizers aapptech LABMATE, Heidolph Synthesis 1, Chemspeed MSW 500, and Buchi Syncore (clockwise from top left).

Peptide sequences were synthesized via the solid phase on a 20 to 50-mmol scale using a homemade manual synthesizer and amino-PEG-PS (0.19 mmol/g, PerSeptive Biosystems) as the solid support. The handle, 6-DMT-aminohex-l-yl hemisuccinate [75], was anchored to the amino-PEG-PS-resin as described previously [76]. The loading of the support was measured by the absorbance of the DMT cation and was 0.1 mmol/g. The elongation of the peptide chain was carried out in DMF using a 5-fold excess of Boc-amino acid, 10-fold excess of DIE A, and 5-fold excess of benzotriazole-1-... 

Manual syntheses were carried out side-by-side in reaction vessels charged, respectively, with Boc-Phe-PEG-PS resin (156 mg,... 

Manual syntheses were carried out side-by-side in two reaction vessels charged, respectively, with Boc-PEG-Nle-PS resin (100 mg, 0.19 mmol/g, 19 )u.mol) and Boc-Nle-PS resin (50 mg, 0.38 mmol/g, 19 /imol). Procedures were modeled on those we reported earlier for this and related sequences [54], but were intentionally not optimized in order to emphasize differences. The )8-carboxyl... 

The coupling times listed in Table 8 are only approximate, and for manual syntheses the actual length of the coupling step is determined by monitoring for imreacted amino groups by the sensitive ninhydrin test. 

Consumables and Automated/Manual Synthesizers. Many manufactures of protected amino acids, resins, coupling agents, and automated/manual synthesizers exist. 

Automated peptide synthesizers are available that can complete one cycle in 40 min and carry out 45 cycles of unattended operation. Though not as efficient as protein synthesis in the body, where enzymes directed by DNA can catalyze assembly of a protein with 150 amino acids in about 1 min, automated peptide synthesis is a far cry from the tedious process of manually synthesizing a peptide step after step. A hallmark example of automated peptide synthesis was the synthesis of ribonuclease, a protein with 124 amino acid residues. The synthesis involved 369 chemical reactions and 11,930 automated steps—aU carried out without isolating an intermediate. The synthetic ribonuclease not only had the same physical characteristics as the natural enzyme, it possessed the identical biological activity as well. The overall yield was 17%, which means that the average yield of each individual step was greater than 99%. 

In this chapter, three inexpensive manual synthesizers for parallel solid phase synthesis that can accommodate three different synthetic scenarios are described. The scenarios differ in the number of compounds synthesized in parallel and in the amount of compound synthesized in one reaction vessel. All instruments are designed to be personal tools for chemists. Operation of the apparatus is very simple, and does not need any special training course, programming, etc. The chemist should have the apparatus available at any time and use them in the same way that one uses other laboratory tools, such as a rotary evaporator, magnetic stirrer, or TLC chamber. 

The selection of a description language or an interface language is difficult in a CAD framework where many tools must communicate and where a user may select to manually synthesize the design. 

Stereodefined PS-ORNs were manually synthesized on solid supports by using the oxazaphospholidine derivatives as monomer units according to the synthetic cycle shown in Scheme 4. Finally, all-(/ p)-[Us]9U (4) and all-(Sp)-[Us]9U (5) were... 

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