Structure-activity relationship studies of novel somatostatin analogs with antitumor activity

Pept Res. 1993 Sep-Oct;6(5):281-8.

Abstract

A series of new somatostatin analogs were synthesized in order to study the relative importance of specific substitutions in relation to selectivity between their endocrine and antitumor effects. Substitutions were carried out in all positions, except for Lys in position 5. Peptides were tested for their ability to inhibit in vitro and in vivo GH release, proliferation of the MCF 7 breast carcinoma cell line and tyrosine kinase activity in the HT 29 human colon carcinoma cell line. Selective biological activity was achieved in GH release and antitumor activity by the different amino acid substitutions. One of the analogs, with a five-residue ring (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-Thr-NH2, TT-232), was unique. It had no GH release inhibitory activity, but did have strong tyrosine kinase inhibitory and antiproliferative effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Cell Division / drug effects
  • Cells, Cultured
  • Growth Hormone / drug effects
  • Humans
  • Molecular Sequence Data
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Rats
  • Somatostatin / analogs & derivatives*
  • Somatostatin / pharmacology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Somatostatin
  • Growth Hormone
  • Protein-Tyrosine Kinases