Reversible acetylation of histone and nonhistone proteins plays pivotal role in cellular homeostasis. Dysfunction of histone acetyltransferases (HATs) leads to several diseases including cancer, neurodegenaration, asthma, diabetes, AIDS, and cardiac hypertrophy. We describe the synthesis and characterization of a set of p300-HAT-specific small-molecule inhibitors from a natural nonspecific HAT inhibitor, garcinol, which is highly toxic to cells. We show that the specific inhibitor selectively represses the p300-mediated acetylation of p53 in vivo. Furthermore, inhibition of p300-HAT down regulates several genes but significantly a few important genes are also upregulated. Remarkably, these inhibitors were found to be nontoxic to T cells, inhibit histone acetylation of HIV infected cells, and consequently inhibit the multiplication of HIV.

Single-molecule surface-enhanced Raman scattering (SM-SERS) is one of the vital applications of plasmonic nanoparticles. The SM-SERS sensitivity critically depends on plasmonic hot-spots created at the vicinity of such nanoparticles. In conventional fluid-phase SM-SERS experiments, plasmonic hot-spots are facilitated by chemical aggregation of nanoparticles. Such aggregation is usually irreversible, and hence, nanoparticles cannot be re-dispersed in the fluid for further use. Here, we show how to combine SM-SERS with plasmon polariton-assisted, reversible assembly of plasmonic nanoparticles at an unstructured metal-fluid interface. One of the unique features of our method is that we use a single evanescent-wave optical excitation for nanoparticle assembly, manipulation and SM-SERS measurements. Furthermore, by utilizing dual excitation of plasmons at metal-fluid interface, we create interacting assemblies of metal nanoparticles, which may be further harnessed in dynamic lithography of dispersed nanostructures. Our work will have implications in realizing optically addressable, plasmofluidic, single-molecule detection platforms.

The vicinity of metallic nanostructures that provides intense optical fields is termed as "hot spot". Any molecule in close proximity to these hot spots will give rise to an increased surface-enhanced Raman spectroscopic (SERS) signal. We have synthesized Ag core-Au shell (core-shell) nanoparticles (NP) with nanopores, which act as hot spots in the SERS measurements. We have demonstrated a large enhancement in SERS studies of various molecules using core-shell NP with hot spots, which is better than using silver nanoparticles. The core-shell NP with hot spots can be used for ultratrace analysis of important biomolecules such as histone acetyltranferase p300, a human transcriptional coactivator protein. The core-shell NP does not change the biomolecule's physical and chemical property upon adsorption, which makes it biocompatible. The coreshell NP carrying hot spots with high SERS enhancement would be ideally suited for in vivo studies of biological systems.

Surface enhanced Raman scattering (SERS) is an optical spectroscopy technique with single molecule sensitivity and chemical specificity. The electromagnetic enhancement mechanism of SERS is facilitated by the localized surface plasmons of metallic nanostructures utilized in experiments. The magnitude of the local optical field created by the plasmonic nanostructure depends on parameters such as size, shape, morphology, arrangement, and local environment of the nanostructure. By tuning these parameters, electromagnetic hot spots can be created to facilitate ultra-sensitive, subwavelength SERS detection platforms. In recent years, there have been a number of innovations in nanofabrication and synthesis of plasmonic nanostructures. This has led to a variety of plasmonic nano-architectures that can be harnessed for SERS. Recently investigated plasmonic nanostructures in the context of SERS include nanosphere dimers, individual nanocubes, nanotriangular arrays, nano-pyramid shells, individual and assembly of nanorods, nanowires, and nanotips, and some unconventional nano-architectures. Challenges in fundamental and application aspects of SERS remain for future research.

Reversible acetylation of nucleosomal histones and nonhistone proteins play pivotal roles in the regulation of all the DNA templated phenomenon. Dysfunction of the enzymes involved in the acetylation/deacetylation leads to several diseases. Therefore, these enzymes are the targets for new generation therapeutics. Here, we report the synthesis of trifluoromethyl phenyl benzamides and their effect on histone acetyltransferase (HAT) activity of p300. One of these benzamides, CTPB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide), was discovered as a potent activator of the p300 HAT activity. We have found that pentadecyl hydrocarbon chain of CTPB is required to activate the HAT only under certain context. Furthermore, our results show that the relative position of -CF 3 and -Cl in CTB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-benzamide) is also very critical for the activation. Surface-enhanced Raman spectroscopy (SERS) of p300 and the HAT activator complexes evidently suggest that the activation of HAT activity is achieved by the alteration of p300 structure. Therefore, apart from elucidating the chemical basis for small molecule mediated activation of p300, this report also describes, for the first time, Raman spectroscopic analysis of the complexes of histone-modifying enzymes and their modulators, which may be highly useful for therapeutic applications.