Synthesis peptides’ multiple solid phase

Lebl, M., Stierandova, A., Eichler, J., et al. (1992) An automated multiple solid phase peptide synthesizer utilizing cotton as a carrier. In Innovation and Perspectives in Solid Phase Peptide Synthesis (Epton, R., ed.). Intercept Limited, Andover, UK, pp. 251-257. 

Wafers and Capsules. Another solution of compartmentalization of resin beads into permeable containers was reported by Beattie and Frost, who invented porous wafers that housed insoluble supports for the multiple solid-phase synthesis of oligonucleotides and peptides. The porous wafer was made from a Teflon ring covered on both sides by a porous Teflon membrane to form a cylindrical permeable container. The use of wafers was reduced to practice in a specialized column-based oligonucleotide synthesizer. ... 

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. 

In 1985 Houghton introduced his tea bag method for the rapid solid phase multiple peptide synthesis. In this technique the beads are contained within a porous polypropylene bag. All the reactions, including deprotections, are... 

Pessi et al. 68 prepared a different multiple antigen peptide employing the continuous-flow polypeptide procedure 69 for the solid-phase peptide synthesis. The resultant one-directional, octaantigen, polypeptide cascade 37 is depicted in Figure 4.2 and was characterized by gel permeation chromatography (GPC), FAB MS, and amino acid ratio analysis. 

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],... 

Besides classical resin beads, other polymeric carriers were also used for the synthesis ofpeptide libraries in various formats. Poly aery late-grafted polypropylene pins were used for the synthesis of the first combinatorial chemical library [1,2], This type of support continues to be heavily used in multiple peptide [27] and non-peptide [28] library synthesis. Cellulose paper, originally used by Frank et al. as a solid-phase support for oligodeoxy-ribonucleotide synthesis [29], has also been used as the support for multiple SPOT synthesis of peptide libraries [30,31], Polystyrene-grafted polyethylene film (PS-PE) may also be used in combinatorial peptide library synthesis [32], The specific feature of the membrane type of carrier is its dividability. This feature has been used for the synthesis of libraries with a nonstatistical distribution of library members, where no compound is missing and none is represented more than once [33],... 

Krchnak, V., Vagner, J., and Mach, O. (1989) Multiple continuous-flow solid-phase peptide synthesis. Synthesis of an HIV antigenic peptide and its omission analogues. Int. J. Peptide Prot. Res. 33, 209-213. 

Krchnak, V. and Vagner, J. (1990) Color-monitored solid-phase multiple peptide synthesis under low-pressure continuous flow conditions. Peptide Res. 3, 182-193. 

Figure 5 Chemoenzymatic approaches for the production of novel bioactive compounds. In this example, the enzymatic buildup of the linear precursor of daptomycin by its NRPSs (DptA, DptBC, and DptD) is substituted by solid-phase synthesis (a). By using the 4 Ppan transferase Sfp and the CoA-thioester of the linear peptide, the opo-enzyme PCP-TE and be modified, and after trans-esterification cyclized by the TE domain (b). Because the resulting ho/o-enzyme cannot be modified again, this is a single turnover reaction. Another strategy uses thiophenole-esters of the linear peptides to be cyclized (c). When these compounds are used, no PCP domain is necessary. The TE domain is readily acylated, and regiospecific and stereospecific cyclization toward daptomycin or, depending on the linear peptide provided, toward variants thereof occurs. Because the enzyme is not altered in any way after product release, this setup results in a multiple turnover.

---