The design and synthesis of the peptide analogs described in the study are the beginning steps in the long process of research and development of suitable pharmaceutical agents capable of penetrating a cancer cell membrane to reach the XIAP target and triggering the signaling pathway that causes the death of cancer cells in vivo. While further modifications and studies are needed on these peptide analogs in order to show their practical values as cell permeable anticancer agents, the present study of these analogs is of basic research interest for understanding the role of proline and conformation of prolyl peptide bond in mediating the biological function of a protein. It is known that the two different conformational isomers (cis and trans isomers) of the prolyl peptide bond can mediate distinct function of the protein. Many studies in the past of proline and proline mimics show either a mixture of cis and trans isomers or purely cis isomer. In this study, the proline mimic displayed strictly the trans conformation. The interesting conformational and functional effects of the synthetic unnatural mimic of proline discovered here suggest an alternative probe of prolyl isomerization in biology and that such a proline mimic can be applied to study the role of proline and proline containing sequence in other protein-protein interactions involved in a wide range of biological functions.
Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said "This elegant study by Ziwei Huang and colleagues explores the role of proline containing peptides in inhibiting the anti-apoptotic function of X
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Society for Experimental Biology and Medicine