64830-74-6Relevant academic research and scientific papers
Chlamydocin-hydroxamic acid analogues as histone deacetylase inhibitors
Nishino, Norikazu,Jose, Binoy,Shinta, Ryuzo,Kato, Tamaki,Komatsu, Yasuhiko,Yoshida, Minoru
, p. 5777 - 5784 (2007/10/03)
Chlamydocin-hydroxamic acid analogues were designed and synthesized as histone deacetylase (HDAC) inhibitors based on the structure and HDAC inhibitory activity of chlamydocin and trichostatin A. Chlamydocin is a cyclic tetrapeptide containing an epoxyketone moiety in the side chain that makes it an irreversible inhibitor of HDAC. We replaced the epoxyketone moiety of chlamydocin with hydroxamic acid to design potent and reversible inhibitors of HDAC. In addition, a number of amino-cycloalkanecarboxylic acids (Acc) are introduced instead of the simple amino-isobutric acid (Aib) for a variety of the series of chlamydocin analogues. The compounds synthesized were tested for HDAC inhibitory activity and the results showed that many of them are potent inhibitors of HDAC. The replacement of Aib residue of chlamydocin with an aromatic amino acid enhances the in vivo and in vitro inhibitory activity. We have carried out circular dichroism and molecular modeling studies on chlamydocin-hydroxamic acid analogue and compared it with the solution structure of chlamydocin.
Synthesis of phakellistatin 11: A Micronesia (Chuuk) marine sponge cyclooctapeptide
Pettit,Lippert III,Taylor,Tan,Williams
, p. 883 - 891 (2007/10/03)
The cyclic octapeptide phakellistatin 11 (1), a constituent of The Federated States of Micronesia (Chuuk) marine sponge Phakellia sp., was synthesized using solid-phase techniques. An initial solution-phase synthesis proved to be inadequate owing to spontaneous deprotection of the Fmoc group at the heptapeptide stage. Using the PAL resin attachment and proceeding from Fmoc-Glu-α-allyl ester, linear elongation of the octapeptide was performed until the final unit Pro was added. The allyl ester was removed using Pd0[P(C6H5)3]4. Cleavage of the final Fmoc group and cyclization with PyAOP provided phakellistatin 11 (1) in 17% overall yield. The synthetic specimen of phakellistatin 11 (1) was found to be chemically but not biologically (cancer cell lines) identical to the natural product. The result suggested a conformational difference or more likely the presence of a trace amount of a highly active antineoplastic agent that binds noncovalently to the natural cyclic octapeptide 1.
Specific fragmentation of thioxo peptides facilitates the assignment of the thioxylated amino acid
Pfeifer, Thomas,Schierhorn, Angelika,Friedemann, Rudolf,Jakob, Mario,Frank, Robert,Schutkowski, Mike,Fischer, Gunter
, p. 1064 - 1071 (2007/10/03)
Low-energy collision-induced dissociation (CID) product ion spectra of a series of singly protonated thioxo peptides produced by electrospray ionization (ESI) were obtained by triple-quadrupole tandem mass spectrometry. The principal feature of the spectr
Process for preparing oxazolo?3,2-a!pyrrolo?2,1-c!pyrazine derivatives
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, (2008/06/13)
The present invention provides a novel cyclization process useful for the production of the peptide moiety of an ergotalkaloid.
