abstract in English: |
Neurotensin (NT) is a naturally occurring neurotransmitter that mediates the metabotropic seven-transmembrane G protein-
coupled receptors, namely NTR1s, richly expressed on tumor surface. Therefore, mutated active molecular fragments of NT
that possess selective antagonist or weak agonist properties and the high af
fi
nity to NTR1 have attracted considerable interest
for use in thrombus, in
fl
ammation, and imaging/treatment of tumors. In this work, SERS spectra of three
N
-terminal fragments
of human NT (NT
1-6
,NT
1-8
, and NT
1-11
) and six speci
fi
cally mutated
C
-terminal fragments of human NT, including NT
8-13
, [Dab
9
]
NT
8-13
, [Lys
8
,Lys
9
]NT
8-13
, [Lys
8
-(
W
)-Lys
9
]NT
8-13
, [Lys
9
,Trp
11
,Glu
12
]NT
8-13
, and NT
9-13
, adsorbed onto nanometer-sized colloidal
silver particles in an aqueous solution at pH level of the solution 2 are presented. A comparison was made between the struc-
tures of the native and mutated fragments to determine how changes in peptide length and mutations of the structure
in
fl
uenced the NT adsorption properties. Based on the interpretation of the obtained data, we showed that all of the investi-
gated NT fragments, excluding [Lys
9
,Trp
11
,Glu
12
]NT
8-13
, tended to adsorb on the silver surface mainly through the L-tyrosine
residue and the carboxylate group. The Tyr ring lied more-or-less
fl
at on the silver surface. The hydrogen atom from the
phenol group dissociated upon binding. On the other hand, [Lys
9
,Trp
11
,Glu
12
]NT
8-13
bound to this substrate through the close
to vertical co-pyrrole ring of the indole ring (Trp
11
) and
–
COO
-
.
Comparison of the presented data with those obtained earlier for NT allows to suggest that in the case of naturally
occurring neurotensin, both Tyr residues together with the carboxylate group play crucial role in the binding to the nanome-
ter-sized colloidal silver particles. This geometry of binding forces the NT molecule to lay
fl
at on the surface. |