New monocyclic and acyclic hNK-2 antagonists retaining the beta-turn feature. X-ray and molecular modelling studies.
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.
Altamura
Maria
M
Menarini Ricerche SpA, Via dei Sette Santi 3, 50131 Florence, Italy.
Dapporto
Paolo
P
Fedi
Valentina
V
Giolitti
Alessandro
A
Guerri
Annalisa
A
Guidi
Antonio
A
Maggi
Carlo Alberto
CA
Paoli
Paola
P
Rossi
Patrizia
P
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*
D009842:Oligopeptides; D010456:Peptides, Cyclic; D018041:Receptors, Neurokinin-2