A molecular dynamics simulation investigation of the relative stability of the cyclic peptide octreotide and its deprotonated and its (CF3)-Trp substituted analogs in different solvents

摘要

The cyclic octa-peptide octreotide and its derivatives are used as diagnostics and therapeutics in relation to particular types of cancers. This led to investigations of their conformational properties using spectroscopic, NMR and CD, methods. A CF3-substituted derivative, that was designed to stabilize the dominant octreotide conformer responsible for receptor binding, turned out to have a lower affinity. The obtained spectroscopic data were interpreted as to show an increased flexibility of the CF3 derivative compared to the unsubstituted octreotide, which could then explain the lower affinity.