Keywords: Astins, Biology, Conformation, Non-Coded Amino Acids, Antineoplastic Agent, Aster Tataricus Extract, Astin Derivative, Pentapeptide, Plant Extract, Proline, Unclassified Drug, Animal Cell, Antineoplastic Activity, Article, Asteraceae, Cancer Cell Culture, Chemical Bond, Controlled Study, Crystal Structure, Drug Activity, Drug Conformation, Drug Isolation, Drug Structure, Drug Synthesis, Human, Human Cell, Lymphatic Leukemia, Nonhuman, Nuclear Magnetic Resonance Spectroscopy, Priority Journal, Sarcoma Cell, X Ray Diffraction, Cell Line, Tumor, Crystallography, X-Ray, Drug Screening Assays, Antitumor, Hydrogen Bonding, Inhibitory Concentration 50, Molecular Structure, Biomolecular, Cyclic, Protein Structure, Tertiary, Temperature,
Affiliations: *** IBB - CNR ***
Dipartimento di Chimica Biologica, Universita di Napoli Federico II, Via Mezzocannone 6, 80134 Napoli, Italy
Istituto di Chimica Biomoleculare, CNR, Universita di Roma La Sapienza, 00185 Roma, Italy
Ist. di Biostrutture e Bioimmagini, C.N.R., 80134 Napoli, Italy
Dipto. Sci. e Tech. per l'Ambiente, Universita degli Studi del Molise, 86170 Isernia, Italy
LCM3B, Groupe de Biocristallographie, UHP Nancy I, 54506 Vandoeuvre Lès Nancy, France
References: Not available.
New antitumour cyclic astin analogues: Synthesis, conformation and bioactivity
Astins, antitumour cyclic pentapeptides, were isolated from the Aster tataricus. Their chemical structures, consist of a 16-membered ring system containing a unique beta,gamma-dichlorinated proline [Pro(Cl)(2)], other non-coded amino acid residues and a cis conformation in one of the peptide bonds. The astin backbone conformation, along with the cis peptide bond in which the beta,gamma-dichlorinated proline residue is involved, was considered to play an important role in their antineoplastic activities on sarcoma 180A and P388 lymphocytic leukaemia in mice, but the scope and potential applications of this activity remain unclear. With the aim at improving our knowledge of the conformational properties influencing the bioactivity in this class of compounds, new astin-related cyclopeptides were synthesized differing from the natural products by the presence of some non-proteinogenic amino acid residues: Aib, Abu, -(S)beta(3)-hPhe and a peptide bond surrogate (-SO2-NH-). The analogues prepared c(-Pro-Thr-Aib-beta(3)-Phe-Abu-), c[Pro-Thr-Aib-(S)beta(3)-hPhe-Abu], c[Pro-Abu-Ser-(S)beta(3)-hPhePsi(CH2-SO2-NH)-Abu] and c[Pro-Thr-Aib-(S)beta(3)-hPhePsi(CH2-SO2-NH)-Abu] were synthesized by classical methods in solution and tested for their antitumour effect. These molecules were studied by crystal-state x-ray diffraction analysis and/or solution NMR and MD techniques. Copyright (C) 2003 European Peptide Society and John Wiley Sons, Ltd.
New antitumour cyclic astin analogues: Synthesis, conformation and bioactivity
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(433 views) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 ViewExport to BibTeXExport to EndNote