Solid Phase Polypeptide Synthesis

POLYPEPTIDE SYNTHESIS, SOLID-PHASE METHOD BIBLIOGRAPHY... 

Brazzain. Polypeptide of 54 amino acids, Mr 6473, from the west African tree Pentadiplandra brazzeana (llliaceae). In a 2% solution it is 2000 times sweeter than cane sugar and shows good thermal stability (no loss of activity after 4 h at 80 °C), compare with mo-nellin, thaumatin. B. can also be obtained by synthesis (solid phase method) or biotechnologic ly in genetically engineered Escherichia coli cultures, lit.- Biopolymers 39, 95-101 (1996). PaL WO 9531 547 (publ. 23.11.1995). gen. FEBS Utt. 355,106 ff. (1994). 

The major disadvantage of solid-phase peptide synthesis is the fact that ail the by-products attached to the resin can only be removed at the final stages of synthesis. Another problem is the relatively low local concentration of peptide which can be obtained on the polymer, and this limits the turnover of all other educts. Preparation of large quantities (> 1 g) is therefore difficult. Thirdly, the racemization-safe methods for acid activation, e.g. with azides, are too mild (= slow) for solid-phase synthesis. For these reasons the convenient Menifield procedures are quite generally used for syntheses of small peptides, whereas for larger polypeptides many research groups adhere to classic solution methods and purification after each condensation step (F.M. Finn, 1976). 

Solid phase peptide synthesis (Section 27 18) Method for peptide synthesis m which the C terminal ammo acid is co valently attached to an inert solid support and successive ammo acids are attached via peptide bond formation At the completion of the synthesis the polypeptide is removed from the support... 

One widely used method involving protected compounds is solid-phase synthesis (polymer-supponed reagents). This method has the advantage of requiring only a simple workup by filtration such as in automated syntheses, especially of polypeptides, oligonucleotides, and oligosaccharides. 

ELPs can be produced via chemical synthesis and biosynthetically. For chemical synthesis via solid phase peptide synthesis, the attainable polymer length is limited, and if long polymers with a defined length are required then the biosynthetic approach is more appropriate. An advantage of chemical synthesis is, however, that it enables the facile introduction of functional residues in the polypeptide [27]. 

The techniques for automated solid phase synthesis were first highly developed for polypeptides and the method is abbreviated as SPPS. Polypeptide synthesis requires the sequential coupling of the individual amino acids. After each unit is added, it must be deprotected for use in the next coupling step. 

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