title: Kinetic analysis of the interaction between yessotoxin and analogues and immobilized phosphodiesterases using a resonant mirror optical biosensor.
abstract: Yessotoxin (YTX) is a disulfated polyether toxin produced by phytoplanktonic microalgae from the dinoflagellates group. YTX has structural similarities to maitotoxin or brevetoxins, and the mechanism of action for YTX is specific and related to calcium modulation. Some studies show that YTX decreases adenosine 3',5'-cyclic monophosphate (cAMP) levels in human lymphocytes. This effect is calcium-dependent, and phosphodiesterases (PDEs) seem to be involved. This point was recently confirmed by studying kinetic constants of YTX-PDEs binding. The aim of this work is to compare the ability of YTX and analogues to bind immobilized PDEs by using a resonant mirror biosensor. These instruments measure biomolecular interactions in real time, without labeling, and allow detailed investigation of the reaction kinetics by analysis of the resultant signals. YTX and the derivatives, 45-hydroxyyessotoxin, carboxyyessotoxin, and yessotoxin-45-(S)-a-methoxy-a-trifluormethylphenylacetate, were added over immobilized PDEs. The kinetic constants obtained from these bindings indicate a relationship between toxin structure and affinity. Since the presence of the functional groups in the side chain decreased the toxic YTX effect and the PDEs-YTX association, our results show that the side chain plays an important role in the YTX affinity for PDEs.
authors: Departamento de Farmacología, Departamento de Fisiología, y Area de Apoyo a la Investigación Agrobiológica, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain.
authors: M José
authors: MJ
authors: Pazos
authors: Amparo
authors: A
authors: Alfonso
authors: Mercedes R
authors: MR
authors: Vieytes
authors: Takeshi
authors: T
authors: Yasumoto
authors: Luis M
authors: LM
authors: Botana
mesh_terms: D015374:Biosensing Techniques / Q000379:methods*; D004800:Enzymes, Immobilized / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D015394:Molecular Structure; D008978:Mollusk Venoms; D035964:Oxocins / Q000737:chemistry* / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*
chemical_list: D004800:Enzymes, Immobilized; D004988:Ethers, Cyclic; D008024:Ligands; D008978:Mollusk Venoms; D035964:Oxocins; D010727:Phosphoric Diester Hydrolases; C066632:yessotoxin