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Improvement of drug-like properties of peptides: the somatostatin paradigm. | LitMetric
Importance Of The Field : 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.Areas Covered In This Review : 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.What The Reader Will Gain : These modifications led to enhanced metabolic stability and intestinal permeability. In addition, several analogs exhibited specific receptor subtype activation.Take Home Message : 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.
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