Oligopeptide synthesis

Fig. 5.5 The oligopeptide synthesis at cationic micelles using the condensation agent CDI leads to the intermediate (I), which is in equilibrium with an IV-carboxyanhydride (II). A free primary or secondary amino acid reacts with (II) and forms an amide linkage as well as a carbamide terminus. ...

As early as 1971 Merrifield [227] was keen to show that oligopeptide synthesis on a resin occurred uniformly throughout the swollen bead and he demonstrated... 

Fig. 6.15. Carboxylic acid activation with DCC. [1,3] means the intramolecular substitution of the oxygen atom 01 by the N atom "3" via a cyclic four-membered tetrahedral intermediate. From the point of view of the heteroatoms, this SN reaction corresponds to a migration of the acyl group R-C=0 from the oxygen to the nitrogen. (Examples for amino acid activations in the form of the pentafluorophenyl ester C or the benzotriazolyl ester D are given in Figure 6.32 (oligopeptide synthesis) and Figure 6.31 (dipeptide synthesis), respectively.

The fluorene linker 1.14 (71), which is easily attached to an aminomethyl PS resin, has been used to support C-terminal Boc-proteeted amino acids during oligopeptide synthesis. The cleavage of this linker requires the use of 20% piperidine, or better 20% morpholine at rt over 2 h. 

As solid-phase synthesis basically involves only three types of operations (addition of excess of reagent shaking the beads in the reagent cocktail filtration and washing) machines have been designed to perform solid-phase synthesis automatically (8). Automated oligonucleotide and oligopeptide synthesis has become routine. 

Professor Bruce Merrifield first disclosed the use of a crosslinked polystyrene support as a macroscopic protecting group in oligopeptide synthesis in 1963... 

Uemura, T., Fujimori, M., Lee, H.-H., Ikeda, S., and Aso, K. (1990) Polyethylene glycol-modified papain catalyzed oligopeptide synthesis from the esters of L-aspartic and L-glutamic acids in benzene. Agric. Biol. Chem., 54... 

Li, G Vaidya, A., Xie, W Gao, W and Gross, R.A. (2008) Enzyme-catalyzed oligopeptide synthesis Rapid regioselective oligomerization of L-glutamic acid diethyl ester catalyzed by papain. ACS Symp. Ser., 999,... 

Enzyme-Catalyzed Oligopeptide Synthesis Rapid Regioselective Oligomerization of L-Glutamic Acid Diethyl Ester Catalyzed by Papain... 

Basic to protease catalyzed oligopeptide synthesis is equilibrium- or thermodynamic control to direct reversal of proteolysis . Difficulties encountered include low reaction rates, high stoichiometric amounts of enzyme, and the need to apply direct approaches to shift the reactions towards formation of desired products. Reaction conditions that lead to product precipitation or extraction increase efficiency of the reverse reaction. Kinetically controlled syntheses has proved useful for serine and cysteine proteases that form activated acyl enzyme intermediates during catalysis. This approach generally involves use of activated acyl moieties, such as esters, as donor components which significantly accelerate the reaction rate. This study makes use of principles from both kinetic and thermodynamically controlled reactions in that, reactants are activated by formation of esters and products precipitate fi om reactions. 

Richards A, Gill I, Vulfson E (1993) Continuous enzymatic production of oligopeptides synthesis of an enkephalin pentapeptide in a multistage bioreactor. Enzyme Microb Technol 15(11) 928-... 

G. Li, A. Vaidya, W. Xie, W. Gao and R. A. Gross, Enzyme-Catalyzed Oligopeptide Synthesis Rapid Regioselective Oligomerization of L-Glutamic Acid Diethyl Ester Catalyzed by Papain , in ACS Symposium Series, ed. H. N. Cheng, American Chemical Society, 2008, vol. 999, Polymer Biocatalysis and Biomaterials II, p. 294. 

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