Improvement of drug-like properties of peptides: the somatostatin paradigm

Abstract

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.

Getting in Shape: Controlling Peptide Bioactivity and Bioavailability Using Conformational Constraints

“…Constrained analogues of these hormones became important probes for understanding endocrine signaling pathways and in some cases were developed as pharmaceuticals. A particularly illustrative example is the development of somatostatin analogues, recently reviewed by Ovadia et al 32 Somatostatin, discovered in 1972, is a hormone that counteracts the effects of human growth hormone. 33 Subsequent analysis of the structural and conformational requirements for its activity by Veber, Hirschmann, and colleagues led to the design of potent constrained peptide analogues.…”

Fine‐tuning the π–π Aromatic Interactions in Peptides: Somatostatin Analogues Containing Mesityl Alanine

“…As it seen in the figure, this structure also contains the hairpin, thus indicating that d-Trp8 additionally stabilizes a conformation that already exists in the natural sequence, and it has been suggested to be essential for the biological activity of somatostatin. [18] The Trp8-Lys9 interactions are reflected in the upfield shifted g protons of Lys which are shielded by the aromatic indole ring.…”

Peptidomimetic therapeutics: scientific approaches and opportunities

“…This natural processing can be taken advantage of to develop therapeutics based primarily on the active form of endogenous peptides. For example, octreotide is a truncated analog of somatostatin, with one disulfide bridge in which the D-Trp stabilizes a β-turn conformation around the D-Trp-Lys region, producing a similar effect to the parent compound [10,11]. Moreover, a truncated form of parathyroid hormone, teriparatide, retains only the anabolic effects of the parent compound.…”