title: Identification of first proadrenomedullin N-terminal 20 peptide (PAMP) modulator by means of virtual screening and NMR interaction experiments.
abstract: PAMP (proadrenomedullin N-terminal 20 peptide) is a regulatory peptide that is detected in a large variety of cell types and exerts important biological activities. PAMP acts as a potent angiogenic factor and decorates microtubules in cells from different origins, controlling tubulin polymerization. A high-throughput docking-based virtual screening was performed, followed by a competitive monoclonal antibody assay on selected compounds, and a detailed (1)H, (15)N NMR spectroscopy study. This procedure has allowed us to describe the first small molecule capable of interacting with PAMP and potentially modulate its biological activity. Molecular modeling methods such as docking and molecular dynamics were carried out to obtain a theoretical model of binding mode. Finally a directed in vivo angiogenesis assay (DIVAA) showed that the small molecule by itself has pro-angiogenic properties.
authors.affiliation: Departamento de Química, Facultad de Farmacia, Universidad CEU-San Pablo, Ctra. Boadilla del Monte km 5.6, Urb. Montepríncipe, 28668 Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Roldós
authors.forename: Rodrigo J
authors.initials: RJ
authors.lastname: Carbajo
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Schott
authors.forename: Antonio
authors.initials: A
authors.lastname: Pineda-Lucena
authors.forename: Laura
authors.initials: L
authors.lastname: Ochoa-Callejero
authors.forename: Alfredo
authors.initials: A
authors.lastname: Martínez
authors.forename: Ana
authors.initials: A
authors.lastname: Ramos
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Pascual-Teresa
mesh_terms: D053607:Adrenomedullin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001667:Binding, Competitive; D004353:Drug Evaluation, Preclinical; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D014584:User-Computer Interface
chemical_list: D000911:Antibodies, Monoclonal; D054852:Small Molecule Libraries; D053607:Adrenomedullin