Effect of amino acid modifications on the molecular structure of adsorbed and nonadsorbed bombesin 6–14 fragments on an electrochemically roughened silver surface

Abstract

This work used infrared absorption and Raman spectroscopy to determine the structure of seven modified fragments (residues 6-14 of the polypeptide chain) of bombesin (BN 6 -14 ). The peptides studied are cyclo[D-Phe 6 , These peptides are potent bombesin agonists useful in the treatment of tumors.Surface-enhanced Raman scattering (SERS) spectroscopy was also used to examine the behavior of these molecules on an electrochemically roughened silver surface. The SERS spectra reveal that substituting native amino acids in these molecules with synthetic ones changes their adsorption state slightly on an electrochemically roughened surface of silver. The peptides [D-Tyr 6 , b-Ala 11 , Phe 13 , Nle 14 ]BN 6 -14 and [D-Tyr 6 , b-Phe 11 , Phe 13 , Nle 14 OH]BN 6 -14 tend to adsorb strongly on this surface via C O fragment (∼1400 cm −1 ). The observed medium enhancement of the Trp 8 residue and amide bond Raman signals indicate further interactions between these fragments and the surface. [D-Phe 6 , Leu-NHEt 13 , des-Met 14 ]BN 6 -14 and [D-Cys 6 , Asn 7 , D-Ala 11 , Cys 14 ]BN 6 -14 are shown to be coordinated to the silver through -CONH-, C O, and the indole ring. The strongest SERS bands (∼1506, ∼1275, ∼1149, and ∼1007 cm −1 ) of [D-Phe 6 , Leu 13 --p-chloro-Phe 14 ]BN 6 -14 and [D-Phe 6 , b-Ala 11 , Phe 13 , Nle 14 ]BN 6 -14 suggest that these two peptides bind to the silver via Trp 8 and -CONH-. In the case of cyclo[D-Phe 6 , His 7 , Leu 14 ]BN 6 -14 , the formation of a peptide/Ag complex is confirmed by the strong SERS bands involving Trp 8 and -CONHvibrations, which are accompanied by a SERS signal due to the C O vibrations.For these analogs, the relative potency for inhibition of binding of 125 I-[Tyr 4 ]BN to rat pancreas acini cells was correlated with the behavior of the amide bond on the silver surface, while the contribution of the structural components to the ability to interact with the rGRP-R was correlated with the SERS patterns.

Nociceptin and its natural and specifically‐modified fragments: Structural studies

“…30 This technique can thus be employed to investigate ligand-receptor binding for drugprotein complexes and differences in individual molecules. 20,25 The enormous Raman scattering enhancement results from the strong increase of local electromagnetic fields in close vicinity to metal (i.e., silver, gold, or copper) surfaces that accompanies the excitation of surface plasmon resonances in the metals. 31 The most popular and universal substrate used for SERS is silver, which is usually used as in colloidal suspension.…”

Adsorption of neurotensin‐family peptides on SERS‐active Ag substrates

“…The behavior of peptides at a liquid/solid interface has been generally accepted as an initial approximation in such research. The liquid/solid interface refers to either a water/membrane interface [studied by means of nuclear magnetic resonance (NMR)] or a water/metal interface [studied by means of surface‐enhanced Raman scattering (SERS) because of its molecular selectivity and sub‐monolayer sensitivity] …”

“…The amino acid composition and its sequence are, in general, accepted as determining the adsorption mechanism of the peptides onto a given metal surface. Therefore, analyzing the SERS signal from the adsorbed species (enhancement, broadening, and wavenumber) allows us to understand the possible ways in which a peptide interacts with the surrounding medium, such as how a peptide binds at a solid/liquid interface . One disadvantage of SERS is the difficulty encountered in the band assignments because changes in signal enhancement can be dramatic.…”

Surface‐enhanced Raman spectroscopy for quantitative measurement of lactic acid at physiological concentration in human serum

“…Podstawka et al [16 -18] used SERS spectroscopy of amino acids to distinguish different kinds of functional chemical bonds and investigation of molecular structure adsorbed and nonadsorbed on electrochemically roughened silver surface. [19,20] Seballos et al [21] used silver nanoparticles as a SERS substrate to detect various forms of lysophosphatidic acid (LPA) as a ovarian cancer biomarker. The SERS technique has also been successfully applied in quantitative analysis of biomolecules.…”