One strategy to enhance tumor retention of imaging agents or anti-cancer drugs is rational design of probes that undergo a tumor-specific enzymatic reaction which prevents them from being pumped out of the cell. Here, the anticancer agent olsalazine (Olsa) was conjugated to the cellpenetrating peptide RVRR. Taking advantage of a biologically compatible condensation reaction, Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

In this review article we present a general overview of the recent progress in the newly developing area of the study of protein-ligand interaction by surface enhanced Raman spectroscopy (SERS). Since its first observation in 1977, SERS have been fast developing into an analytical tool for trace detection of molecular entities, particularly in the area of bio-molecule sensing and characterization. Also, with the development of the ability to design a variety of plasmonic structures and to be able to control and tune their plasmonic properties, we have been able to use them as SERS substrates for probing complex materials. Here we describe yet another application of SERS, mainly protein-ligand interaction and its future into drug designing. We start with a general description of the SERS phenomenon. Subsequently we discuss the key spectral features of amino acids, peptides and proteins, and their structural aspects that can be elucidated from the SERS spectra. In the final sections we discuss the application of SERS to the study protein-ligand interaction and its potential role in the area of drug designing.

We demonstrate here a novel high surface area GaN nanowall network substrate with plasmonic Ag nanodroplets, that can be employed as a highly sensitive, reproducible, and charge independent SERS substrate. The uniformity of the size and distribution of the Ag droplets and the absence of linker ligands result in large near-field intensity, while the GaN nanowall network morphology provides multiple reflections for signal enhancement. FDTD calculations simulate the observed hot-spot distribution and reiterate the higher performance of this hybrid substrate over conventional ones. Our studies on oppositely charged proteins provide a proof of concept for employing this as a versatile charge independent label free SERS substrate for trace biomolecule detection.

We demonstrate the use of surface-enhanced Raman spectroscopy (SERS) as an excellent tool for identifying the binding site of small molecules on a therapeutically important protein.As an example, we show the specific binding of the common antihypertension drug felodipine to the oncogenic Aurora A kinase protein via hydrogen bonding interactions with Tyr-212 residue to specifically inhibit its activity. Based on SERS studies, molecular docking, molecular dynamics simulation, biochemical assays, and point mutation-based validation, we demonstrate the surface-binding mode of this molecule in two similar hydrophobic pockets in the Aurora A kinase. These binding pockets comprise the same unique hydrophobic patches that may aid in distinguishing human Aurora A versus human Aurora B kinase in vivo. The application of SERS to identify the specific interactions between small molecules and therapeutically important proteins by differentiating competitive and noncompetitive inhibition demonstrates its ability as a complementary technique. We also present felodipine as a specific inhibitor for oncogenic Aurora A kinase. Felodipine retards the rate of tumor progression in a xenografted nude mice model. This study reveals a potential surface pocket that may be useful for developing small molecules by selectively targeting the Aurora family kinases.vibrational spectroscopy | structure-activity relationship | ligand binding U nderstanding the mechanism of ligand binding to proteins is imperative for designing new molecules or screening potential drug molecules from available databases. We have used surface-enhanced Raman spectroscopy (SERS), which is a highly sensitive technique, to understand the binding of the commonly used hypertension drug, felodipine, to Aurora A kinase. Although NMR (1), X-ray crystallography (2), surface plasmon resonance (3), and fluorescence (4) are experimental techniques used to explore protein-drug interactions and each of these techniques provides unique information about the proteinligand interaction, a common problem of these techniques is the requirement of a high-protein concentration or the incorporation of secondary tagged molecules and a protein size limit. SERS has been traditionally used for the ultrasensitive detection of analytes. However, it can also be used to examine the protein-small molecule interactions and elucidate the mechanism (5-7). A commonly debated aspect is that SERS does not provide complete vibrational information compared with resonant Raman or normal Raman spectroscopy. Despite the limited information from SERS, which can be performed in proteins at extremely low concentrations in their active state, the competitive binding versus noncompetitive binding and specific changes in protein upon ligand binding can be explained. This approach is extremely effective when combined with molecular dynamics (MD) simulations and the structural information of the protein. The usefulness of this combination is that drugs can be screened for therapeutic applications. This paper provid...

Surface enhanced Raman spectroscopy (SERS) has emerged as a promising technique for the rapid and ultrasensitive detection of molecular species such as drugs of abuse in biofluids. Yet, it remains a significant challenge to create a viable screening tool for multiple drug classes, owing to the lack of affinity of certain species for the SERS substrate and to the matrix interference in complex media. Here we report a protein tethering SERS approach, which blends plasmonic enhancement with facile drug binding, to engineer a rapid, label-free and versatile screening tool for narcotics. By exploiting the known binding attributes of human serum albumin, we determine the effective concentration of narcotics present in solution through differential enhancement of the spectral markers. In conjunction with chemometric methods, this approach not only enables unambiguous recognition of different drug classes, such as barbiturates, opiates, amphetamines and benzodiazepines, but also offers a lower limit of detection in comparison to direct SERS application. Through molecular docking simulations, we probe the mechanistic underpinnings of the protein tethering approach paving the way for narcotic detection in clinical samples in the near future.