title: Improvement of drug-like properties of peptides: the somatostatin paradigm.
abstract: BACKGROUND
  Peptides are promising candidates as therapeutic agents due to their wide involvement in physiological processes. However, their often non-selective activity and their poor drug-like properties, mainly their inherent low stability to enzymatic degradation and poor oral bioavailability, limit their clinical potential. Somatostatin is a peptide hormone involved in many different biological functions. The role of its five different receptor subtypes and their interplay in medicinal processes is only partially understood. In addition, it suffers from poor drug-like properties.
  
  
  METHODS
  We review several promising chemical modifications, including head-to-tail and backbone cyclization as well as N-methylation, which were applied throughout the years in the development of various somatostatin analogs.
  
  
  RESULTS
  These modifications led to enhanced metabolic stability and intestinal permeability. In addition, several analogs exhibited specific receptor subtype activation.
  
  
  CONCLUSIONS
  The results presented in this review suggest a potential use of these chemical modifications in order to achieve required characteristics for a bioactive peptide, mainly for clinical usage.
authors: The Hebrew University of Jerusalem, Department of Pharmaceutics, Jerusalem 91120, Israel.
authors: Oded
authors: O
authors: Ovadia
authors: Sarit
authors: S
authors: Greenberg
authors: Burkhardt
authors: B
authors: Laufer
authors: Chaim
authors: C
authors: Gilon
authors: Amnon
authors: A
authors: Hoffman
authors: Horst
authors: H
authors: Kessler