Structural Determinants in the Binding of BB2 Receptor Ligands: In Silico, X-Ray and NMR Studies in PD176252 Analogues.
BACKGROUND
The mammalian bombesin receptor family comprises three G proteincoupled receptors: the neuromedin B receptor, the gastrin-releasing peptide receptor (BB2), and the bombesin receptor subtype 3. BB2 receptor plays a role in gastrointestinal functions; however, at present the role of this subtype in physiological and pathological conditions is unknown due to the lack of specific binders for all subclasses of bombesin receptors.


RESULTS
Here, we present a study focused on the properties of the peptoid bombesin antagonist called PD176252, and other structural analogues with the aim to elucidate causes of their different affinity towards the BB2 receptor.


CONCLUSIONS
By means of computational techniques, based on QSAR, docking and homology building, supported by experimental data (X-ray diffraction and NMR spectroscopy) fresh insights on binding modes of this class of biological targets were achieved.
Dipartimento di Farmacia- Scienze del Farmaco, Universita degli Studi di Bari "Aldo Moro", Via Orabona 4, 70125, Bari, Italy.
Antonio
A
Carrieri
Dipartimento di Farmacia-Scienze del Farmaco, Universita degli Studi di Bari "Aldo Moro", Via Orabona 4, 70125, Bari, Italy.
Enza
E
Lacivita
Centre for Biomolecular Science, University of Nottingham, Nottingham, United Kingdom.
Benny Danilo
BD
Belviso
Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Via Amendola 122/o, 70126, Bari, Italy.
Rocco
R
Caliandro
Dipartimento di Ingegneria Civile, Ambientale, del Territorio, Edile e di Chimica (DICATECh), Politecnico di Bari, Via Orabona 4, 70125, Bari, Italy.
Piero
P
Mastrorilli
Dipartimento di Ingegneria Civile, Ambientale, del Territorio, Edile e di Chimica (DICATECh), Politecnico di Bari, Via Orabona 4, 70125, Bari, Italy.
Vito
V
Gallo
Dipartimento di Farmacia-Scienze del Farmaco, Universita degli Studi di Bari "Aldo Moro", Via Orabona 4, 70125, Bari, Italy.
Mauro
M
Niso
Dipartimento di Farmacia-Scienze del Farmaco, Universita degli Studi di Bari "Aldo Moro", Via Orabona 4, 70125, Bari, Italy.
Marcello
M
Leopoldo
D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D008024:Ligands; D008279:Magnetic Resonance Imaging; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D018004:Receptors, Bombesin / Q000737:chemistry* / Q000378:metabolism*
D007211:Indoles; D008024:Ligands; D018004:Receptors, Bombesin; C116774:PD 176252
Bombesin receptor; Docking; NOESY.; PD176252; QSAR; X-ray