VIPER is a genetically encoded peptide tag for fluorescence and electron microscopy.

Many discoveries in cell biology rely on making specific proteins visible within their native cellular environment. There are various genetically encoded tags, such as fluorescent proteins, developed for fluorescence microscopy (FM). However, there are almost no genetically encoded tags that enable cellular proteins to be observed by both FM and electron microscopy (EM).

Multifunctional Pt(II) Reagents: Covalent Modifications of Pt Complexes Enable Diverse Structural Variation and In-Cell Detection.

To enhance the functionality of Pt-based reagents, several strategies have been developed that utilize Pt compounds modified with small, reactive handles. This Account encapsulates work done by us and other groups regarding the use of Pt(II) compounds with reactive handles for subsequent elaboration with fluorophores or other functional moieties. Described strategies include the incorporation of substituents for well-known condensation or nucleophilic displacement-type reactions and their use, for example, to tether spectroscopic handles to Pt reagents for in vivo investigation.

Azide vs Alkyne Functionalization in Pt(II) Complexes for Post-treatment Click Modification: Solid-State Structure, Fluorescent Labeling, and Cellular Fate.

Tracking of Pt(II) complexes is of crucial importance toward understanding Pt interactions with cellular biomolecules. Post-treatment fluorescent labeling of functionalized Pt(II)-based agents using the bioorthogonal Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has recently been reported as a promising approach. Here we describe an azide-functionalized Pt(II) complex, cis-[Pt(2-azidobutyl)amido-1,3-propanediamine)Cl2] (1), containing the cis geometry and difunctional reactivity of cisplatin, and present a comparative study with its previously described alkyne-functionalized congener.

An alkyne-appended, click-ready Pt(II) complex with an unusual arrangement in the solid state.

To better understand the range of cellular interactions of Pt(II) -based chemotherapeutics, robust and efficient methods to track and analyze Pt targets are needed. A powerful approach is to functionalize Pt(II) compounds with alkyne or azide moieties for post-treatment conjugation through the azide-alkyne cycloaddition (click) reaction. Herein, we report an alkyne-appended cis-diamine Pt(II) compound, cis-[Pt(2-(5-hexynyl)amido-1,3-propanediamine)Cl2] (1), the X-ray crystal structure of which exhibits a combination of unusual radially distributed CH/π(C≡C) interactions, Pt-Pt bonding, and NH:O/NH:Cl hydrogen bonds.

Convenient detection of metal-DNA, metal-RNA, and metal-protein adducts with a click-modified Pt(II) complex.

cis-[Pt(2-azido-1,3-propanediamine)Cl2] is a reagent for high-yield post-treatment fluorescent labelling of Pt(II) biomolecular targets using click chemistry and exhibits a bias in conformational isomers in the context of duplex DNA. Pt-protein adducts are detected using BSA as a model. Following in vivo treatment, long-lived Pt-RNA adducts are detected on ribosomal RNA.

Platinum-RNA modifications following drug treatment in S. cerevisiae identified by click chemistry and enzymatic mapping.

With the importance of RNA-based regulatory pathways, the potential for targeting noncoding and coding RNAs by small molecule therapeutics is of great interest. Platinum(II) complexes including cisplatin (cis-diamminedichloroplatinum(II)) are widely prescribed anticancer compounds that form stable adducts on nucleic acids. In tumors, DNA damage from Pt(II) initiates apoptotic signaling, but this activity is not necessary for cytotoxicity (e.

Picazoplatin, an azide-containing platinum(II) derivative for target analysis by click chemistry.

Despite the broad use of platinum-based chemotherapeutics, identification of their full range of cellular targets remains a significant challenge. In order to identify, visualize, and isolate cellular targets of Pt(II) complexes, we have modified the chemotherapeutic drug picoplatin with an azide moiety for subsequent click reactivity. The new compound picazoplatin readily binds DNA and RNA oligonucleotides and undergoes facile post-labeling click reactions to alkyne-fluorophore conjugates.

Large enhancements in optoelectronic efficiencies of nano-plastically stressed conjugated polymer strands.

The photoluminescence (PL) of well dispersed molecules of a conjugated polymer, poly[2-methoxy-5-((2'-ethylhexyl)oxy)-1,4-phenylene-vinylene] (MEH-PPV), in an optically inert matrix manifested dramatic increases when the individual molecular strands were fully stretched. The PL increase rose with stretching and may reach several folds when the mechanical strain of the matrix polymer went beyond 550%. Strong polarization effects indicate that stretching individual polymer chains was responsible for the PL enhancement.

Combination treatment for menstrual migraine and dysmenorrhea using sumatriptan-naproxen: two randomized controlled trials.

Objective: To evaluate the efficacy and tolerability of sumatriptan-naproxen during the mild pain phase of a single menstrual migraine attack associated with dysmenorrhea.

Methods: Two replicate randomized, multicenter, double-blind, placebo-controlled, trials of adults with menstrual migraine and dysmenorrhea were conducted. Participants treated their menstrual migraine attack during the mild pain phase (within 1 hour of onset) with sumatriptan 85 mg and naproxen sodium 500 mg in a single fixed-dose formulation (sumatriptan-naproxen) or placebo.

Effects of gender on relapse prevention in smokers treated with bupropion SR.

Background: Recent data suggest that women smokers respond differently than men to cessation pharmacotherapies, particularly nicotine replacement therapy (NRT). Lower abstinence and higher relapse rates are often reported for women treated with NRT. Gender effects for those treated with non-nicotinic, bupropion-hydrochloride sustained release for relapse prevention have not been studied.