HYBRID MOLECULES CONTAINING AMIDATED POLYPEPTIDE BINDING LIGANDS

摘要

Disclosed are hybrid molecules containing a first part, a second part and third part connected by covalent bonds. The first part contains a chemical entity to be introduced into an animal cell. The second part contains a polypeptide effective to translocate the chemical entity across the cytoplasmic membrane and into the cytoplasm of the animal cell. The third part contains a C-terminal amidated polypeptide ligand effective to cause the hybrid molecule to bind to the animal cell. The amidated hybrid molecules exhibit greater biological activity than non-amidated counterparts. Preferred hybrid molecules are fusion toxins which contain an amidated neuropeptide, e.g., substance P or gastrin releasing peptide. Methods of preparing the hybrid molecules, which in preferred embodiments are prepared enzymatically by peptidlglycine- alpha -amidating monooxygenase, are also disclosed. Further disclosed are methods of using the hybrid molecules for medical purposes, such as in the fields of diagnostics and therapeutics.