TAILIEUCHUNG - Báo cáo khoa học: Inhibition of polyamine and spermine oxidases by polyamine analogues

Polyamine oxidase (PAO) and spermine oxidase (SMO) are involved in the catabolism of polyamines – basic regulators of cell growth and prolifer-ation. The discovery of selective inhibitors of PAO and SMO represents an important tool in studying the involvement of these enzymes in polyamine homeostasis and a starting point for the development of novel antineoplas-tic drugs. | ềFEBS Journal Inhibition of polyamine and spermine oxidases by polyamine analogues Marzia Bianchi1 Fabio Polticelli1 Paolo Ascenzi1 2 Maurizio Botta3 Rodolfo Federico1 Paolo Mariottini1 and Alessandra Cona1 1 Dipartimento di Biologia Universita Roma Tre Italy 2 Laboratorio Interdipartimentale di Microscopia Elettronica University Roma Tre Italy 3 Dipartimento Farmaco Chimico Tecnologico Universita di Siena Italy Keywords polyamines polyamine analogue inhibitors polyamine oxidase spermine oxidase Correspondence A. Cona Dipartimento di Biologia Universita Roma Tre Viale Guglielmo Marconi 446 I-00146 Rome Italy Fax 39 06 55176321 Tel 39 06 55176360 E-mail cona@ Received 24 November 2005 revised 11 January 2006 accepted 16 January 2006 doi Polyamine oxidase PAO and spermine oxidase SMO are involved in the catabolism of polyamines - basic regulators of cell growth and proliferation. The discovery of selective inhibitors of PAO and SMO represents an important tool in studying the involvement of these enzymes in polyamine homeostasis and a starting point for the development of novel antineoplastic drugs. Here a comparative study on murine PAO mPAO and SMO mSMO inhibition by the polyamine analogues 1 8-diaminooctane 1 12-diaminododecane N-prenylagmatine G3 guazatine and N N1-bis 2 3-butadienyl -1 4-butanediamine MDL72527 is reported. Interestingly 1 12-Diaminododecane and G3 behave as specific inhibitors of mPAO values of Ki for mPAO inhibition being lower than those for mSMO inactivation by several orders of magnitude. The analysis of molecular models of mPAO and mSMO indicates a significant reduction of the hydrophobic pocket located in maize PAO MPAO at the wider catalytic tunnel opening. This observation provides a rationale to explain the lower affinity displayed by G3 guazatine and MDL72527 for mPAO and mSMO as compared to MPAO. The different behaviour displayed by 1 12-diamino-dodecane towards mPAO and mSMO reveals the .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• immune system
• Antimicrobial
• biosynthesis
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• Crystal structure
• bacteria
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine