Racemization studies in peptide synthesis through the separation of protected epimeric peptides by reversed-phase high performance liquid chromatography.
Separation of protected epimeric peptides, Z-Gly-Xaa-Xbb-OMe (where Xaa and Xbb = chiral amino acid residues), by reversed-phase HPLC was utilized for studying racemization in peptide synthesis. Thus, the following factors which might affect the extent of racemization during the coupling by the carbodiimide method were investigated: the combination of amino acid residues to be coupled, coexisting tertiary amine salts, and the relative configuration of the amino acid residues. The following points were revealed: the combination of bulky residues at the coupling site results in extensive racemization in a polar solvent such as DMF, the amine hydrochlorides cause less racemization than the p-toluene-sulfonates in DMF, and the influence of relative configuration differs depending on the solvent and the individuality of the amino components. Furthermore, the racemization-suppressing effect of some additives in the carbodiimide method was reevaluated by employing the same procedure.
Miyazawa
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T
Department of Chemistry, Faculty of Science, Konan University, Kobe, Japan.
Otomatsu
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Yamada
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Kuwata
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S
D000596:Amino Acids / Q000737:chemistry; D002234:Carbodiimides; D002851:Chromatography, High Pressure Liquid; D004126:Dimethylformamide; D005663:Furans; D007536:Isomerism; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D011487:Protein Conformation; D012997:Solvents
D000596:Amino Acids; D002234:Carbodiimides; D005663:Furans; D010455:Peptides; D012997:Solvents; C018674:tetrahydrofuran; D004126:Dimethylformamide