Synthesis continued peptide

Synthesis of Peptide. There is continual progress ia the improvement of instmments and reagents for peptide synthesis, especially "soHd phase polymerization" (90) (see Proteins). This method is suitable for the synthesis of peptides with 20 30 amino acid units. 

Figure 12.2 A hypothetical synapse where co-existence of peptides and classical transmitters occurs. A is a classical transmitter whereas B and C are peptides. The slow synthesis of peptides and the need for axonal transport may mean that in active neurons, the classical transmitter may be released under all conditions, but the peptide(s) may require higher intensities of stimulation for release and be depleted if the neuron continues to fire for long periods. Competition for peptidases can lead to changes in levels of two co-released peptides. At the postsynaptic site, the receptor mechanisms of the co-existing transmitters can also produce complex changes in neuronal activity...

M Beyermann, M Bienert, H Niedrich, LA Carpino, D Sadat-Aalaee. Rapid continuous peptide synthesis via FMOC amino acid chloride coupling and (4-aminome-thyl(piperidine deblocking. J Org Chem 55, 721, 1990. 

Continuous reactions at the side chains of branched or comblike structured polymers play an important role in the solid-phase synthesis of peptides or oli-go-nucleotides. 

Formation of an amide bond (peptide bond) will take place if an amine and not an alcohol attacks the acyl enzyme. If an amino acid (acid protected) is used, reactions can be continued to form oligo peptides. If an ester is used the process will be a kinetically controlled aminolysis. If an amino acid (amino protected) is used it will be reversed hydrolysis and if it is a protected amide or peptide it will be transpeptidation. Both of the latter methods are thermodynamically controlled. However, synthesis of peptides using biocatalytic methods (esterase, lipase or protease) is only of limited importance for two reasons. Synthesis by either of the above mentioned biocatalytic methods will take place in low water media and low solubility of peptides with more than 2-3 amino acids limits their value. Secondly, there are well developed non-biocatalytic methods for peptide synthesis. For small quantities the automated Merrifield method works well. 

As beta-lactam antibiotics continue to be a major contributor to human health preservation, research on the biosynthesis of penicillin, an almost ancient drug, continues to open up roads to new technologies and perspectives. The provision of precursor peptides to be transformed enzymatically with chemically unachieved efficiency into mono- or bicyclic antibiotics has been termed by Jack Baldwin and colleagues the irreversible commitment of metabolic carbon to the secondary metabolism [1]. The synthesis of such peptides is indeed performed by a remarkable class of synthetases which, in contrast to the protein-synthesizing machinery, have been termed a nonribosomal system or nonribosomal peptide synthetases (NRPS) [2]. These peptide synthetases have been shown to catalyze the irreversible synthesis of peptides differing both in sequence and stmctural variability, thus extending the scope of directly gene-encoded poly-... 

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],... 

The synthesis continues with repetition ofthese two steps until the peptide chain is complete. The peptide is cleaved from the resin, usually with HF in pyridine or CF3SO2OH in CF3CO2H and given a final purification from small amounts of peptides of the wrong sequence by chromatography, usually HPLC. 

SYNTHESIS OF, peptides (Continued) methylguanidine. 1,3-Thiazolidine-2-thione. 

The synthesis continues like common solid phase peptide synthesis, including final deprotection and cleavage. 

Ai -Bsmoc amino acid fluorides are useful for solid phase and, in particular, rapid continuous solution synthesis of peptides. An example of the latter procedure is given. 

In synthesis of peptides containing adjacent sterically hindered or N-substituted amino acids, complete chain propagation may not be obtainable. More accessible sites on the resin may continue to grow well, whereas more hindered sites may fail, but couple in a later step with a less hindered amino acid, e.g. glycine. In these cases, dehberate termination by acetylation can prevent contanoination of the product by omission sequences which may be more difficult to remove during purification than a shorter acetylated peptide. Both acetylimidazole and acetic anhydride have been used successfully for such acetylation acetylimidazole is the more reactive of these two reagents. 

Although the solid-phase technique was first developed for the synthesis of peptide chains and has seen considerable use for this prupose, it has also been used to synthesize chains of polysaccharides and polynucleotides in the latter case, solid-phase synthesis has almost completely replaced synthesis in solution. The technique has been applied less often to reactions in which only two molecules are brought together (nonrepetitive syntheses), but many examples have been reported. Combinatorial chemistry had its beginning with the Merrifield synthesis, particularly when applied to peptide synthesis, and continues as an important part of modem organic chemistry. ... 

If synthesis of the first -1020 amino acids of a protein does not produce a functional signal peptide directing the protein to the membrane compartment of the ER, then protein synthesis continues in the cytoplasm on membrane-free ribosomes and the protein is released into the cytosol. These newly synthesized cytosolic proteins have a variety of possible destinations, including the cytoplasm, the nucleus, mitochondria,... 

A Kramer, R Volkmer-Engert, R Malin, U Reineke, J Schneider-Mergener. Simultaneous synthesis of peptide libraries on single resin and continuous cellulose membrane supports examples for the identification of protein, metal and DNA binding peptide mixtures. Peptide Res 6 314-319, 1993. 

Scheme 3 Wikberg s continuous flow synthesis of peptides using cotton disks in a split and pool strategy...

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