An Assessment of the Conformational Profile of Neuromedin B Using Different Computational Sampling Procedures

Abstract

Neuromedin B (NMB) (Minamino et al., 1983), a ten residue (GNLWATGHFM-NH2, Figure 1) neuropeptide, belongs to the ranatensin subfamily of bombesin-like peptides (Erspamer, 1980) which exhibits a wide range of biological responses in the central nervous system and gastrointestinal tract including thermoregulation (Marki et al., 1981), stimulation of the secretion of gastrointestinal hormones (Ghatei et al., 1982), regulation of smooth muscle contraction (Erspamer, 1988), the ability to function as a growth factor in small cell lung cancer cells and murine 3T3 cells (Corps et al., 1985; Cuttitta et al., 1985; Moody et al., 1985). Its mechanism of action involves the initial binding to the three cell surface receptors (OhkiHamazaki, 2000) with different pharmacological profile: the neuromedin B receptor (NMB-R or bb1) (Wada et al., 1991), the gastrin-releasing peptide receptor (GRP-R, or bb2) (Corjay et al., 1991), and bombesin receptor subtype 3 (BRS-3, or bb3) (Gorbulev et al., 1992). NMB binds to NMB-R with highest affinity, GRP-R with lower affinity and BRS-3 with lowest affinity (Mantey et al., 1997).