Researchers made 11 versions of a brain peptide called DSIP and tested them in mice with lung cancer that spreads to other organs. A few of the new versions worked better than the original peptide at slowing the spread of the cancer, and they also helped restore normal immune cell activity. The benefits depended on small changes at the start of the peptide, showing that shape matters more than just making the peptide harder to break down.

With the aim to investigate structure-functional relations of DSIP, 11 DSIP analogues were tested on antimetastatic activity, among them five new analogues, differing in positions 2 and 6 of the DSIP amino acid sequence were synthesized by the solid-phase method using Fmoc-approach. Experiments on C57B1 mice with metastatic Lewis lung carcinoma showed some analogues to be more efficient as antimetastatic agents then DSIP after i.v. (50 micrograms/kg) administration. Normalization of neuroendocrine status and activity of peritoneal, alveolar and spleen macrophages after the DSIP and some analogues injections in mice with metastatic Lewis lung carcinoma took place. Antimetastatic action of DSIP derivatives is considerably affected by structural changes, especially in the N-terminal part. Conformational factors rather than enhanced enzymatic resistance are essential for antimetastatic response.