Aptamers recognize their targets with extraordinary affinity and specificity. The aptamer-based therapeutic, Macugen, is derived from a modified 2′fluoro pyrimidine RNA inhibitor to vascular endothelial growth factor (VEGF) and is now being used to treat the wet form of age-related macular degeneration. This VEGF ₁₆₅ aptamer binds specifically to the VEGF ₁₆₅ isoform, a dimeric protein with a receptor-binding domain and a heparin-binding domain (HBD). To understand the molecular recognition between VEGF and this aptamer, binding experiments were used to show that the HBD contributes the majority of binding energy in the VEGF ₁₆₅ –aptamer complex. A tissue culture-based competition assay demonstrated that the HBD effectively competes with VEGF ₁₆₅ for aptamer binding in vivo . Comparison of NMR spectra revealed that structural features of the smaller HBD–aptamer complex are present in the full-length VEGF ₁₆₄ –aptamer complex. These data show that the HBD provides the binding site for the aptamer and is the primary determinant for the affinity and specificity in the VEGF ₁₆₅ –aptamer complex.

In nature, complex and well-defined structures are constructed by the self-assembly of biomolecules. It has been shown that β-peptide foldamers can mimic natural peptides and self-assemble into three-dimensional molecular architectures thanks to their rigid and predictable helical conformation in solution. Using shorter foldamers, which can be prepared more easily than longer ones, to form such architectures is highly desirable, but shorter foldamers have been overlooked due to the seemingly inferior number of intramolecular hydrogen bonds to stabilize a folded state in solution. Here we report that a β-peptide tetramer, although it lacks full helical propensity in solution, does self-assemble to form well-defined microtubes with rectangular cross-section by evaporation-induced self-assembly.

The pyrimidine(6–4)pyrimidone photoproduct [(6–4) adduct] is one of the major photoproducts induced by UV irradiation of DNA and occurs at TpT sites. The (6–4) adduct is highly mutagenic and leads most often to a 3′ T → C transition with 85% replicating error frequency [LeClerc, J. E., Borden, A. & Lawrence, C. W. (1991) Proc. Natl. Acad. Sci. USA 88, 9685–9689]. To determine the origin of the specific 3′ T → C transition of the (6–4) adduct, we have used experimental NMR restraints and molecular dynamics to determine the solution structure of a (6–4)-lesion DNA decamer duplex that contains a mismatched base pair between the 3′ T residue and an opposed G residue. Normal Watson–Crick-type hydrogen bonding is retained at the 5′ T of the lesion site. The O2 carbonyl of the 3′ T residue forms hydrogen bonds with the imino and amino protons of the opposed G residue. This potential hydrogen bonding stabilizes the overall helix and restores the highly distorted conformation of the (6–4) adduct to the typical B-form-like DNA structure. This structural feature can explain the marked preference for the insertion of an A residue opposite the 5′ T and a G residue opposite the 3′ T of the (6–4) lesion during trans-lesion synthesis. Thus these insertions yield the predominant 3′ T → C transition.

Breast cancer is one of the major causes of mortality in women worldwide. The current treatments available are radiation therapy (RT), surgery, endocrine (hormone) therapy (ET), chemotherapy (CT), and targeted therapy. These treatments are associated with certain side effects that demand the use of natural compounds due to their lower to negligible side effects. One such category of natural compounds is alkaloids. Alkaloids are a group of natural compounds that have gained widespread attention due to their use as potential therapeutics. Alkaloids exert anti-inflammatory and antiviral properties along with antimicrobial activities. In the current review, 12 alkaloids are reviewed in detail for their potential in treating breast cancer. These alkaloids have been shown to induce apoptosis, decrease tumor volume, inhibit cell proliferation and migration, and induce autophagy and they can also be used as a component of combination therapy. This review provides comprehensive information on the in vitro and in vivo therapeutic abilities of alkaloids to counteract breast cancer.