Receptor affinity of neurotensin message segment immobilized on liposome

Neurotensin derivatives having a dioctadecyl group were synthesized and immobilized on DMPC liposome to construct a multivalent-ligand system. The derivatives are Ac-Glu[N(C18H37)2]-(Sar-Sar-Pro)n-Arg-Arg-Pro-Tyr-Ile-Leu-OH (D3nNT, n = 0,1,2,3), where a dioctadecyl group was connected to the N-terminal side of neurotensin 8-13 fragment directly or through a hydrophilic and flexible spacer chain of different lengths. The derivatives were spontaneously immobilized on DMPC liposome upon incubation overnight. The receptor affinity of the derivatives increased significantly upon immobilization on liposome. The maximum affinity was obtained by D9NT immobilized on DMPC liposome at the molar ratio of DMPC and D9NT of 200. This affinity is slightly better than the neurotensin 8-13 fragment, the message segment of the derivatives. The fluorescent microscopy using rhodamine-labelled liposome revealed that the multivalent-ligand system binds to specific receptors without dissociation of the derivative from DMPC liposome.