Comparison of two solid-phase peptide syntheses of a 32-amino acid carboxyl-terminal fragment of human parathyroid hormone,hPTH-(53–84) |
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Authors: | Michael Rosenblatt Geoffrey W. Tregear Gary L. Shepard George A. Tyler Marta Veroni John T. Potts |
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Affiliation: | 1. Endocrine Unit, Department of Medicine, Harvard Medical School and the Massachusetts General Hospital, Boston, Massachusetts 02114, USA;2. The Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia |
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Abstract: | Two approaches were employed in separate syntheses of the carboxyl-terminal third of human parathyroid hormone, hPTH-(53–84). The standard N,N′-dicychohexylcarbodiimide coupling method was compared to amino acid incorporation using in situ and preformed symmetrical anhydrides of tert-butoxycarbonyl-amino acids. Also, protection of the δ-carboxyl function of glutamic acid by the benzyl group was compared to protection by the chlorobenzyl group. The products of both synthetic strategies were chemically evaluated. The purified synthetic hormone fragment prepared by standard methods was found to be homogeneous and virtually identical to the native carboxyl-terminal region of the hormone by the analytical criteria employed. However, the synthetic product resulting from use of symmetrical anhydrides was heterogeneous. Also, several practical advantages were noted for amino acid incorporation by the standard method. Since the symmetrical anhydride method has been found to be extremely successful as an approach to the synthesis of other peptides, this report indicates that the choice of symmetrical anhydride versus standard coupling methods may in part be determined by the sequence selected for synthesis. In addition, both approaches produced a large number of side products. Hence, methods selected for purification of the desired product were essential to the successful preparation of this synthetic peptide. |
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