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Binding properties of a highly potent and selective iodinated aminopeptidase N inhibitor appropriate for radioautography

Aminopeptidase N (APN) is a zinc metallopeptidase involved in the inactivation of biologically active peptides. The knowledge of its precise distribution is crucial to investigate its physiological role. This requires the use of appropriate probes such as the recently developed highly potent and sel...

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Detalles Bibliográficos
Autores principales: Noble, Florence, Luciani, Nathalie, Da Nascimento, Sophie, Laï-Kuen, René, Bischoff, Laurent, Chen, Huixiong, Fournié-Zaluski, Marie-Claude, Roques, Bernard P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141570/
https://www.ncbi.nlm.nih.gov/pubmed/10664461
http://dx.doi.org/10.1016/S0014-5793(99)01645-2
Descripción
Sumario:Aminopeptidase N (APN) is a zinc metallopeptidase involved in the inactivation of biologically active peptides. The knowledge of its precise distribution is crucial to investigate its physiological role. This requires the use of appropriate probes such as the recently developed highly potent and selective radiolabeled APN inhibitor 2(S)‐benzyl‐3‐[hydroxy(1′(R)‐aminoethyl)phosphinyl]propanoyl‐l‐3‐[(125)I]iodotyrosine ([(125)I]RB 129). Its binding properties were investigated using rat brain homogenates (K (d)=3.4 nM) or APN expressed in COS‐7 cells (K (d)=0.9 nM). The specific binding was 95% at [K (d)], and preliminary autoradiography in intestine is promising. The decreased affinity of [(125)I]RB 129 (=10(−6) M) for the E(350)D APN mutant, supports the critical role of E(350) in the amino‐exopeptidase action of APN.