Katı fazda peptid sentezi

Abstract

In this work, the syntheses of three new peptides (XXIV-Xxvr, Table 2.2) , each containing 39 amino acids, are reported. N-t-butyloxy-carbonyl-p-choloro-L-phenylalanine (XXVIIa) and N-t-htyloxycarbmyl-L-2- aminoheptanoic acid (XXVIIIa), necessary for the above syntheses, have also been prepared for the first the. These peptides are analogs of the "nonheme" peptide of cytochrame c which is a protein found in all cells having a nucleus.Cytochrame c from different species are known to show differences in their amino acid sequences. Horse heart cytochrame c (XXI) consists of one "heme c" group and 104 amino acid residues in a single polypeptide chain. The 66-104 fragment of this chain, ccmtaining 39 amino acids, is known as the nonheme peptide (XXIII) . The peptides synthesized differ from this nonheme peptide (XXIII) only in one position. In the first peptide (XXIV,) tyrosine-67 has been replaced by p-chloro-l-phenylalanine; in the second one, (XXIV) tyrosine-67 by p-chloro-L-phenylalanine; and in the third one (XXVI)', lyshe-79 by L-2-amhoheptanoic acid. Combination of these analogs with the native 1-65 heme peptide (XXIIb) of horse heart cytochrame c (XXI) wold yield semi-synthetic proteins. Studies on these semi-synthetic proteins would then give information about cytochrane c, which functions as an electron-transport, protein in the cells for the reduction of oxygen to water and the synthesis of adenosine triphosphate. Specifically, this information would be useful in detemining the mechanism of oxidation-reduction reactions , of cytochrame c and in understanding the structure-function relationships in the molecule. In the solid phase method applied in the synthesis of each peptide, the amino acid (104) which contains the free carboxyl group of the peptide has been attached to a polimer, known as the solid support, by forming a covalent bond between this carboxyl group and the polimer; and then all the other mino acids (103-66) have been added one at a time in a stepwise manner to this amino acid on the polimer. After the completion of addition, the free peptide has been released into solution by cleavage of the covalent bond between the peptide chain and the polimer. Finally, the peptide, obtahed in the solid form by lyophilization of the solution, has been purified by gel chromatography.