title: New monocyclic and acyclic hNK-2 antagonists retaining the beta-turn feature. X-ray and molecular modelling studies.
abstract: The human tachykinin NK-2 (hNK-2) receptor is considered a promising target for relevant pathologies at the respiratory, gastrointestinal and genitourinary level. With the aim of reducing the complexity of existing peptide antagonists, two series of hNK-2 receptor antagonists were designed, with the support of modelling, and synthesized. The X-ray structure determination of two compounds, each belonging to one of the two series, allowed the experimental validation of the initial rationale. In addition, it has been found that the two series share a beta-turn structure, a key feature for binding the hNK-2 receptor.
authors.affiliation: Menarini Ricerche SpA, Via dei Sette Santi 3, 50131 Florence, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Altamura
authors.forename: Paolo
authors.initials: P
authors.lastname: Dapporto
authors.forename: Valentina
authors.initials: V
authors.lastname: Fedi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giolitti
authors.forename: Annalisa
authors.initials: A
authors.lastname: Guerri
authors.forename: Antonio
authors.initials: A
authors.lastname: Guidi
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Maggi
authors.forename: Paola
authors.initials: P
authors.lastname: Paoli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rossi
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D008958:Models, Molecular; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*
chemical_list: D009842:Oligopeptides; D010456:Peptides, Cyclic; D018041:Receptors, Neurokinin-2