Recent Developments in Depsipeptide Research

Abstract

This review focuses on the major developments in depsipeptide research since 1995. Depsipeptides are bio-oligomers composed of hydroxy and amino acids linked by amide and ester bonds. Many depsipeptides show very promising biological activities, including anticancer, antibacterial, antiviral, antifungal, anti-inflammatory, and anti-clotting or anti-antherogenic properties. In this report depsipeptides exhibiting these properties are discussed. Their isolation, structural determination, and notable structural features are discussed, but their biological properties and therapeutic potentials are emphasized. Depsipeptides have shown the greatest therapeutic potential as anticancer agents. Four depsipeptides have entered clinical trials for cancer treatment. Among the antiviral compounds discovered, the callipeltins and the quinoxapeptins are particularly promising due to their inhibitory activities against HIV. These compounds have the potential to be developed as anti-AIDS drugs or to serve as lead compounds for the discovery of structurally related anti-AIDS compounds. Antifungal compounds, such as the jaspamides, may lead to therapies against many of the opportunistic infections that accompany AIDS. Anti-inflammatory compounds such as SCH217048 act as neurokinin antagonists and may lead to anti-inflammatory treatments. Some depsipeptides such as micropeptins and A90720A have been found to be effective plasmin inhibitors, which have implications as treatments for cardiovascular diseases. Compounds such as SCH58149 help control the levels of HDL and LDL.

AT514, a cyclic depsipeptide from Serratia marcescens, induces apoptosis of B-chronic lymphocytic leukemia cells: interference with the Akt/NF-κB survival pathway

“…12 The depsipeptide FR901228, for example, is a histone deacetylase inhibitor that induces cell death in many solid tumors, T cell leukemias and multiple myeloma. 13 FR901228 also induces apoptosis of B-CLL cells and is currently under clinical trials for treatment of this malignancy.…”

Identification of α- and β-hydroxy acid containing cyclodepsipeptides in natural peptide mixtures using negative ion mass spectrometry

“…Among the cyclic peptides, cyclodepsipeptides which contain ester linkages in addition to amide bonds, are widely distributed in nature [6,7]. Both ␣-and ␤-hydroxy acids have been found in cyclodepsipeptides.…”

Sintesis Prekursor Senyawa Beauvericin, Asam (2r)-Asetiloksiisovalerat

“…Minat baru dalam karakterisasi struktur dan farmakologi peptida siklik dan siklodepsipeptida bahan alam ini memiliki sifat biologis berbeda yang dapat berguna dalam perkembangan terapetik (Ballard et al, 2002;Jimeno et al, 2004). Siklodepsipeptida didefinisikan sebagai senyawa yang mengandung satu atau lebih dari asam amino dimana salah satunya diganti dengan asam hidroksi, yang menghasilkan suatu ikatan ester dalam cincin utamanya.…”