http://www.cnr.it/ontology/cnr/individuo/prodotto/ID274322

Site-dependent biological activity of valinomycin analogs bearing derivatizable hydroxyl sites (Articolo in rivista)

Type

Prodotto della ricerca (Classe)
Articolo in rivista (Classe)

Label

Site-dependent biological activity of valinomycin analogs bearing derivatizable hydroxyl sites (Articolo in rivista) (literal)

Anno

2013-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1002/psc.2571 (literal)

Alternative label

Annese, C.; Abbrescia, D. I.; Catucci, L.; D'Accolti, L.; Denora, N.; Fanizza, I.; Fusco, C.; La Piana, G. (2013)
Site-dependent biological activity of valinomycin analogs bearing derivatizable hydroxyl sites
in Journal of peptide science (Print); WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ (Stati Uniti d'America)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Annese, C.; Abbrescia, D. I.; Catucci, L.; D'Accolti, L.; Denora, N.; Fanizza, I.; Fusco, C.; La Piana, G. (literal)

Pagina inizio

751 (literal)

Pagina fine

757 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

http://biblioproxy.cnr.it:2099/store/10.1002/psc.2571/asset/psc2571.pdf?v=1&t=hp90q890&s=6fa8706f6059e6e8a9e22b2eb8c403b6cbd29b2b (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

19 (literal)

Rivista

Journal of peptide science (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

7 (literal)

Note

ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Univ Bari A Moro, Dipartimento Chim, I-70126 Bari, Italy. CNR Ist Composti Organometall ICCOM, Bari Sect, I-70126 Bari, Italy. Univ Bari A Moro, Dipartimento Biosci Biotecnol & Biofarmaceut, I-70126 Bari, Italy. Univ Bari A Moro, Dipartimento Farm Sci Farmaco, I-70126 Bari, Italy (literal)

Titolo

Site-dependent biological activity of valinomycin analogs bearing derivatizable hydroxyl sites (literal)

Abstract

Valinomycin (VLM, 1) is a K+ ionophore cyclodepsipeptide capable of depolarizing mitochondria and inducing apoptosis to several mammalian cell types, including a number of tumor cell lines. With the aim of creating VLM-based ligand-targeted anticancer drugs that may selectively convey VLM to pathological cells, we have previously introduced derivatizable hydroxyl handles into the VLM structure, allowing to access a three-entity library of monohydroxyl VLMs (HyVLMs) bearing the OH group at the isopropyl side chain of a d-Hyi, d-Val, or l-Val residue (analogs 2-4, respectively). Herein, the levels of bioactivity retained by the conjugable HyVLMs have been assessed on the basis of their ability to alter the functionality of isolated rat-liver mitochondria. Experiments run with HyVLMs in the range 1-10nM and in 20 or 125mM KCl medium show that the hydroxyl group reduces the potency of HyVLMs relative to VLM to an extent that depends upon the molecular site involved in the hydroxylation. On the other hand, estimation of the stability constants of complexes (in methanol at 25 degrees C) of each analog with Na+, K+, and Cs+ reveals that HyVLMs nicely retain the VLM binding features, except for a moderate increase in the stability of Na+ complexes. These findings, along with pertinent structural considerations, suggest that the incorporation of OH into the VLM structure might actually have altered its K+ transporting ability across mitochondrial membranes. Besides facing new aspects of VLM structure-activity relationship, these studies set the basis for the rational design of ligand-HyVLMs conjugates through derivatization of hanging OH group. (literal)

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