Probing the Peptidylglycine alpha-Hydroxylating Monooxygenase Active Site with Novel 4-Phenyl-3-butenoic Acid Based Inhibitors (Articolo in rivista)

Type

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

Label

• Probing the Peptidylglycine alpha-Hydroxylating Monooxygenase Active Site with Novel 4-Phenyl-3-butenoic Acid Based Inhibitors (Articolo in rivista) (literal)

Anno

• 2010-01-01T00:00:00+01:00 (literal)

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

• 10.1002/cmdc.201000214 (literal)

Alternative label

• Langella, E ; Pierre, S; Ghattas, W; Giorgi, M; Reglier, M; Saviano, M; Esposito, L; Hardre, R (2010)
  Probing the Peptidylglycine alpha-Hydroxylating Monooxygenase Active Site with Novel 4-Phenyl-3-butenoic Acid Based Inhibitors
  in ChemMedChem (Print)
  (literal)

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

• Langella, E ; Pierre, S; Ghattas, W; Giorgi, M; Reglier, M; Saviano, M; Esposito, L; Hardre, R (literal)

Pagina inizio

• 1568 (literal)

Pagina fine

• 1576 (literal)

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

• 5 (literal)

Rivista

• ChemMedChem (Rivista)

Note

• ISI Web of Science (WOS) (literal)

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

• CNR, Ist Biostrutture & Bioimmagini, I-80134 Naples, Italy Aix Marseille Univ, Inst Sci Mol Marseille, Equipe BiosCiences, CNRS,UMR 6263, F-13397 Marseille 20, France Aix Marseille Univ, CNRS, FR1739, F-13397 Marseille 20, France (literal)

Titolo

• Probing the Peptidylglycine alpha-Hydroxylating Monooxygenase Active Site with Novel 4-Phenyl-3-butenoic Acid Based Inhibitors (literal)

Abstract

• Specific inhibition of the copper-containing peptidylglycine alpha-hydroxylating monooxygenase (PHM), which catalyzes the post-translational modification of peptides involved in carcinogenesis and tumor progression, constitutes a new approach for combating cancer. We carried out a structure-activity study of new compounds derived from a well-known PHM substrate analogue, the olefinic compound 4-phenyl-3-butenoic acid (PBA). We designed, synthesized, and tested various PBA derivatives both in vitro and in silico. We show that it is possible to increase PBA affinity for PHM by appropriate functionalization of its aromatic nucleus. Compound 2d, for example, bears a meta-benzyloxy substituent, and exhibits better inhibition features (K(i) = 3.9 mu m, k(inact)/K(i) = 427 M(-1) s(-1)) than the parent PBA (K(i) = 19 mu m, k(inact)/K(i) = 82 M(-1) s(-1)). Docking calculations also suggest two different binding modes for PBA derivatives; these results will aid in the development of further PHM inhibitors with improved features. (literal)

Prodotto di

• Institute of Crystallography (IC) (Istituto)
• Institute of biostructure and bioimaging (IBB) (Istituto)

Autore CNR

• MICHELE SAVIANO (Persona)
• LUCIANA ESPOSITO (Persona)
• EMMA LANGELLA (Persona)

Incoming links:

Autore CNR di

• MICHELE SAVIANO (Persona)
• LUCIANA ESPOSITO (Persona)
• EMMA LANGELLA (Persona)

Prodotto

• Institute of Crystallography (IC) (Istituto)
• Institute of biostructure and bioimaging (IBB) (Istituto)

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

• ChemMedChem (Rivista)