Plitidepsin (Aplidin[R]), a cyclic
depsipeptide, has been evaluated in a phase III clinical trial for multiple myeloma [12].
Kobashi et al., "FK228 (
depsipeptide) as a natural prodrug that inhibits class I histone deacetylases," Cancer Research, vol.
Thompson, "A phase II study of
depsipeptide in refractory metastatic renal cell cancer," Clinical Genitourinary Cancer, vol.
Li et al., "Histone deacetylase inhibitor
depsipeptide activates silenced genes through decreasing both CpG and H3K9 methylation on the promoter," Molecular and Cellular Biology, vol.
Another antitumor
depsipeptide, kahalalide F (Cruz et al.
Briefly, a
depsipeptide derivative of Abeta(1-42) was synthesized and, after purification, it was used in lyophilized form.
Thiocoraline, a novel
depsipeptide with antitumor activity produced by a marine Micromonospora.
The problems of the "difficult" peptide synthesis are usually solved by (a) adding chaotropic salts or solvents [26, 27], (b) elevation of reaction mixture temperature via conventional heating or microwave irradiation [28-30], (c) use of more efficient catalysts of 9-fluorenyl(methoxycarbonyl) (Fmoc) N-terminal amino-protecting group removal and amino acid acylation [31, 32], and (d) prevention of the aggregation via introducing amido bond modifying groups [25, 33], isoacyl
depsipeptide structures [34], and pseudoproline residues [35].
Chin et al., "Phase I study of
depsipeptide in pediatric patients with refractory solid tumors: a children's oncology group report," Journal of Clinical Oncology, vol.