A photoinduced, benzyne click reaction.

The [3 + 2] cycloaddition of azides and alkynes has proven invaluable across numerous scientific disciplines for imaging, cross-linking, and site-specific labeling among many other applications. We have developed a photoinitiated, benzyne-based [3 + 2] cycloaddition that is tolerant of a variety of functional groups as well as polar, protic solvents. The reaction is complete on the minute time scale using a single equivalent of partner azide, and the benzyne photoprecursor is stable for months under ambient light at room tempurature. Herein we report the optimization and scope of the photoinitiated reaction as well as characterization of the cycloaddition products.

N-activated ß-lactams as versatile reagents for acyl carrier protein labeling.

Acyl carrier proteins are critical components of fatty acid and polyketide biosynthesis. Their primary function is to shuttle intermediates between active sites via a covalently bound phosphopantetheine arm. Small molecules capable of acylating this prosthetic group will provide a simple and reversible means of introducing novel functionality onto carrier protein domains. A series of N-activated ß-lactams are prepared to examine site-specific acylation of the phosphopantetheine-thiol. In general, ß-lactams are found to be significantly more reactive than our previously studied ß-lactones. Selectivity for the holo over apo-form of acyl carrier proteins is demonstrated indicating that only the phosphopantetheine-thiol is modified. Incorporation of an N-propargyloxycarbonyl group provides an alkyne handle for conjugation to fluorophores and affinity labels. The utility of these groups for mechanistic interrogation of a critical step in polyketide biosynthesis is examined through comparison to traditional probes. In all, we expect the probes described in this study to serve as valuable and versatile tools for mechanistic interrogation.

Direct acylation of carrier proteins with functionalized beta-lactones.

As the key component of many biosynthetic assemblies, acyl-carrier proteins offer a robust entry point for introduction of small molecule probes and pathway intermediates. Current labeling strategies primarily rely on modifications to the phosphopantetheine cofactor or its biosynthetic precursors followed by attachment to the apo form of a given carrier protein. As a greatly simplified alternative, direct and selective acylation of holo-acyl-carrier proteins using readily accessible beta-lactones as electrophilic partners for the phosphopantetheine-thiol has been demonstrated.

Anticancer activities of cranberry phytochemicals: an update.

Studies employing mainly in vitro tumor models show that extracts and compounds isolated from cranberry fruit (Vaccinium macrocarpon) inhibit the growth and proliferation of several types of tumor including breast, colon, prostate, and lung. Proanthocyanidin oligomers, flavonol and anthocyanin glycosides and triterpenoids are all likely contributors to the observed anticancer properties and may act in a complementary fashion to limit carcinogenesis. Possible chemopreventive mechanisms of action by cranberry phytochemicals include induction of apoptosis in tumor cells, reduced ornithine decarboxylase activity, decreased expression of matrix metalloproteinases associated with prostate tumor metastasis, and anti-inflammatory activities including inhibition of cyclooxygenases. A review of recent studies suggests a potential role for cranberry as a dietary chemopreventive and provides direction for future research.