Protein synthesis from solid phase peptide synthesi

Protein Synthesis using Peptide Fragments Derived from Solid Phase Peptide Synthesis... 

In addition to incorporating the 4-(2-aminoethyl)dibenzofuran-6-propanoic acid template into small peptides where a reverse turn is desired, we have also recently incorporated this template into a mini-protein called the PIN WW domain. WW domains have a three-stranded antiparallel p-sheet structure that mediates intracellular protein-protein interactions. 31 Substitution of this 3-turn mimetic into loop 1 of the PIN WW domain leads to a folded, three-stranded, antiparallel p-sheet structure with a stability indistinguishable from that of the all a-amino acid sequence. The template-incorporated PIN WW domain (11) was synthesized by an Fmoc-based solid-phase peptide synthesis strategy (Scheme 8), utilizing N-Fmoc-protected 4-(2-aminoethyl)dibenzofuran-6-propanoic acid 10. 11 The synthesis of 10, similar to that of 8, has been published.1 1 ... 

In the Merrifield method, the C-terminal amino acid is covalently attached to a solid support contained in a column. Each N-terminal blocked amino acid is added one at a time, along with other needed reagents, so the protein is synthesized from the C-terminal end to the N-terminal end. Notice that this is opposite to the way proteins are synthesized in nature (from the N-terminal end to the C-terminal end Section 27.13). Because it uses a solid support and is automated, Merrifield s method of protein synthesis is called automated solid-phase peptide synthesis. 

The utility of this ligation approach has been demonstrated through the convergent syntheses of therapeutic peptides (ovine-corticoliberin and Forteo) and the human erythrocyte acylphosphatase protein ( 11 kDa) [82]. The requisite peptide salicylaldehyde ester precursor is prepared in an epimerization-free manner via Fmoc-solid-phase peptide synthesis. This approach was also used for the synthesis of Daptomycin (Fig. 14), a lipodepsipeptide isolated firom Streptomyces roseoporus which was obtained from a soil sample from Mount Ararat (Turkey) [83]. 

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