ABSTRACT The synthesis of three peptide sequences of Thrombospondin, by solid phase methodology, is described. The presence of an Asp-Gly pair in two of these sequences promoted the formation of aspartimide as the major side reaction. The presence of the aspartimide was evidenced by the hydroxylamine reaction and the stability of linear parent peptides as well as that of cyclic by-products was controlled by HPLC after incubation of the samples at pH=4.5 and 7.4. Moreover, a CD study of the linear and aspartimide containing peptides was carried out to determine the conformational tendencies of all of them. The biological activity of these peptides was determined in cell proliferation models using three human carcinoma cell lines: breast (MCF7), pancreas (Bx-PC3) and colon (HT-29). Results indicate that linear peptides have no activity as far as the proliferation was concerned in the cell lines above described. On the contrary those containing a cyclic aspartimide residue in the middle of the sequence promoted a soft but significant positive effect on cell proliferation, except for Bx-PC3 cells.
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