Polymerization processes peptide synthesis

Peptide synthesis was amenable to solid-phase techniques since the process was repetitive. The C-terminal amino acid is attached to polymeric surface and the peptide chain is assembled via a two-step process coupling of the incoming amino acid that has the alpha-amino group protected... 

The conversion of the amino group in amino acids into a t-butyloxycarbonyl group is a process which is widely used in automated peptide synthesis carried out on solid (polymeric) supports (solid phase synthesis the Merrifield technique).230... 

Automated polymer-based synthesis comes into its own when a stepwise polymerization is required with precise control over the addition of particular monomers in a specific sequence. This is almost a definition of peptide synthesis, Nature attaches each amino acid to a different polymer (transfer RNA) and uses a computer program (the genetic code) to assemble the polymers in the right order so that the amino acids can be joined together while bound to another polymer (a ribosome). No protection of any functional groups is necessary in this process. 

Stem et al. developed a batch-processing approach to mechanized peptide synthesis using polymeric active esters105). The procedure consisted of the following three consecutive steps without isolation of the intermediate compounds ... 

The formation of a highly reactive nitrene can be used for immobilization of a polymer. The in-situ crosslinking of polymers is induced by exposure to UV light (350 nm) of polymers prepared by free-radical polymerization of the desired monomer to which a pyridinium ylid-type monomer is added in small amounts. Depending on the final product requirements, more than one monomer can be incorporated. This flexibility allows one to tailor a process in a very simple manner. The immobilization of reactive polymer on various surfaces produces a template from which numbers of separation can be performed ion exchange, reverse phase, affinity, or chiral chromatography. The support can also be used in product preparation such as DNA/peptide synthesis. 

The histories of phase transfer catalysis, Merrifield peptide synthesis, and supported enzymes suggest that synthetic processes using polymeric catalysts may be adopted in commercial production, but that methods for multistep syntheses are less likely. The reasons for this prediction follow. 

It is not surprising that a process that involves proton abstraction is influenced by the polarity of the solvent. Base catalyzed racemization of active esters is fast in polar solvents such as dimethylformamide and slow in non-polar media, for instance in toluene. It is rather unfortunate that such non-polar solvents are more often than not impractical in peptide synthesis. The poor solubility of most blocked intermediates in the commonly used organic solvents severely limits their use and in the preparation of larger peptides indeed dimethylformamide is most frequently applied. The problem of solubility is less serious in solid phase peptide synthesis (cf. Chapter X), where no real solvent is needed but merely a medium in which the polymeric support properly swells. This function is fulfilled by dichloromethane its effect on racemization lies between the extremes mentioned. 

Direct autocatalysis occurs in biological polymerizations, such as DNA and RNA replication. In normal biological processes, RNA is produced from DNA. The RNA acts as the carrier of genetic information in peptide synthesis. However, RNA has been found to be able to replicate itself, for example, with the assistance of the Q/li replicase enzyme. Bauer and McCaskill have created traveling fronts in populations of short self-replicating RNA variants (Bauer ct ah, 1989 McCaskill and Bauer, 1993). If a solution of monomers of triphosphorylated adenine, gua-... 

Synthetic peptide-based polymers are not new materials homopolymers of polypeptides have been available for many decades, yet have only seen limited use in materials applications. However, new methods in chemical synthesis have made possible the preparation of increasingly complex polypeptide sequences of controlled molecular weight that display properties far superior to ill-defined homopolypeptides. Examination of the different methods for polypeptide synthesis reveals the limitations of these techniques for preparation of well-defined copolymers. Conventional solid-phase peptide synthesis is neither useful nor practical for direct preparation of large polypeptides (> 100 residues) due to unavoidable deletions and truncations that result from incomplete deprotection and coupling steps. The most economical and expedient process for synthesis of long polypeptide chains is the polymerization of a-amino acid N-carboxyanhydrides (NCAs)... 

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