ABSTRACT
Molecular photonics is a rapidly developing and multi-disciplinary field of research involving the construction of molecular assemblies comprising photoactive building blocks that are responsive to a light stimulus. A salient challenge in this field is the controlled assembly of these building blocks with nanoscale precision. DNA exhibits considerable promise as an architecture for the templated assembly of photoactive materials. In this Concept Article we describe the progress that has been made in the area of DNA photonics, in which DNA acts as a platform for the construction of optoelectronic assemblies, thin films and devices.
Subject(s)
DNA/chemistry , Microarray Analysis/instrumentation , Nanostructures/chemistry , Optics and Photonics/instrumentation , Animals , Equipment Design , Humans , Microarray Analysis/methods , Optics and Photonics/methodsABSTRACT
Based on a split-and-mix strategy, a library of trimeric Polyamide Amino Acids (PAA) incorporating four different amino acids (Lys, Ala, Arg, and Phe) has been prepared. Screening of the batches for HIV TAR RNA binding in a fluorescent assay allowed the identification of several components that interact with TAR RNA at a micromolar concentration, with a good TAR versus tRNA specificity. Some of these compounds compete efficiently with the association of TAR and Tat protein. In cell cultures, these compounds display a moderate antiviral activity, associated nevertheless with some toxicity. Overall, these results confirm that this new family can be a basis for the design of novel RNA targeting drugs.
Subject(s)
Amino Acids/chemistry , Anti-HIV Agents/chemistry , HIV Long Terminal Repeat , Nylons/chemistry , RNA, Viral/chemistry , Amino Acid Sequence , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Fluorescence Resonance Energy Transfer , Ligands , Nylons/chemical synthesis , Nylons/pharmacology , RNA, Viral/metabolism , tat Gene Products, Human Immunodeficiency Virus/chemistry , tat Gene Products, Human Immunodeficiency Virus/metabolismABSTRACT
This communication introduces a new class of promising RNA ligands, named polyamide amino acids (PAA), which are able to bind a targeted bulged stem-loop RNA fragment (HIV-1 TAR RNA) with micromolar affinities and with specificity comparative to dsDNA and tRNA; both the affinity and the specificity of PAA for TAR depend on their length and on the nature of the amino acid residues.
Subject(s)
Amino Acids/chemistry , Amino Acids/metabolism , Nylons/chemistry , Nylons/metabolism , RNA/chemistry , RNA/metabolism , Ligands , Molecular Structure , Nylons/chemical synthesisABSTRACT
Imidazoquinoxaline and pyrazoloquinoxaline derivatives, analogues of imiquimod, were synthesized, and their in vitro cytotoxic and pharmacodynamic activities were evaluated. In vitro cytotoxicity studies were assessed against melanoma (A375, M4Be, RPMI-7591), colon (LS174T), breast (MCF7), and lymphoma (Raji) human cancer cell lines. In vivo studies were carried out in M4Be xenografted athymic mice. EAPB0103, EAPB0201, EAPB0202, and EAPB0203 showed significant in vitro activities against A375 compared to fotemustine and imiquimod used as references. These compounds were 6-110 and 2-45 times more active than fotemustine and imiquimod, respectively. EAPB0203 bearing phenethyl as substituent at position 1 and methylamine at position 4 showed the highest activity. EAPB0203 has also a more potent cytotoxic activity than imiquimod and fotemustine in M4Be and RPMI-7591 and interesting cytotoxic activity in other tumor cell lines tested. In vivo, EAPB0203 treatment schedules caused a significant decrease in tumor size compared to vehicle control and fotemustine treatments.
