Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities. In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.

A review on the dietary flavonoid kaempferol.

2.1.8. Michael Reaction 2245 2.1.9. Others 2247 2.2. Cyclization Reactions 2248 2.2.1. Carbon Diels−Alder Reactions 2248 2.2.2. Aza-Diels−Alder Reactions 2252 2.2.3. Other Hetero-Diels−Alder Reactions 2255 2.2.4. Ionic Diels−Alder Reaction 2256 2.2.5. 1,3-Dipolar Cycloadditions 2256 2.2.6. Other Cycloaddition Reactions 2258 2.2.7. Prins-type Cyclization 2259 2.3. Friedel−Crafts Acylation and Alkylation 2259 2.4. Baylis−Hillman Reaction 2263 2.5. Radical Addition 2264 2.6. Heterocycle Synthesis 2267 2.7. Diazocarbonyl Insertion 2270 3. C−X (X ) N, O, P, Etc.) Bond Formation 2271 3.1. Aromatic Nitration and Sulfonylation 2271 3.2. Michael Reaction 2272 3.3. Glycosylation 2273 3.4. Aziridination 2275 3.5. Diazocarbonyl Insertion 2276 3.6. Ring-Opening Reactions 2277 3.7. Other C−X Bond Formations 2280 4. Oxidation and Reduction 2280 4.1. Oxidation 2280 4.2. Reduction 2281 5. Rearrangement 2283 6. Protection and Deprotection 2285 6.1. Protection 2285 6.2. Deprotection 2288 7. Polymerization 2291 8. Miscellaneous Reactions 2291 9. Lanthanide(II) Triflates in Organic Synthesis 2295 10. Conclusion 2295 11. Acknowledgment 2295 12. References 2295

Rare-earth metal triflates in organic synthesis

Ribosome-inactivating proteins from plants

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.22881

Hepatitis B: the virus and disease.

The diverse cellular and biological functions of the nuclear factor kappa B (NF-κB) pathway, together with the catastrophic consequences of its aberrant regulation, demand specific and highly regulated control of its activity. As described in this review, regulation of the NF-κB pathway is brought about through multiple post-translational modifications that control the activity of the core components of NF-κB signaling: the IκB kinase (IKK) complex, the IκB proteins and the NF-κB subunits themselves. These regulatory modifications, which include phosphorylation, ubiquitination, acetylation, sumoylation and nitrosylation, can vary, depending on the nature of the NF-κB-inducing stimulus. Moreover, they frequently have distinct, sometimes antagonistic, functional consequences and the same modification can have different effects depending on the context. Given the important role of NF-κB in human health and disease, understanding these pathways will not only provide valuable insights into mechanism and function, but could also lead to new drug targets and the development of diagnostic and prognostic biomarkers for many pathological conditions.

Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway

Ricin A-chain is an N-glycosidase that attacks ribosomal RNA at a highly conserved adenine residue. The enzyme is representative of a large family of medically significant proteins used in the design of anticancer agents and in the treatment of HIV infection. The x-ray structure has been used as a guide to create several active site mutations by directed mutagenesis of the cloned gene. Glu177 is a key catalytic residue, and conversion to Gln reduces activity 180-fold. Asn209 is shown to participate in substrate binding by kinetic analysis. Conversion to Ser increases Km sixfold but has no effect on kcat. Conversion of Tyr80 and Tyr123 to Phe decreases activity by 15- and 7-fold respectively. A mechanism of action is proposed that involves binding of the substrate adenine in a syn configuration that resembles the transition state; the putative oxycarbonium ion is probably stabilized by interaction with Glu177.

Site‐directed mutagenesis of ricin A‐chain and implications for the mechanism of action

https://www.cell.com/structure/pdf/S0969-2126(00)00505-0.pdf

The 2.0 Å Crystal Structure of Cephalosporin Acylase

Active site residues of ricin A chain were analyzed by site-directed mutagenesis and X-ray diffraction to help assess their roles in the mechanism of action of this toxic N-glycosidase enzyme. Arg180 is thought, from X-ray studies, to protonate the adenine substrate at N3; this facilitates bond cleavage and is crucial to the mechanisms of action. The residue was converted to Gln and initial rate data measured. Km for the mutant is not significantly affected, increasing only 2-fold. The kcat, however, is decreased approximately 1000-fold. This is consistent with a simple interpretation that Arg180 is involved more in transition state stabilization than in substrate binding. Tyrosines 80 and 123 are known from X-ray models to stack on either side of the substrate adenine ring. When they were each converted to serine overall activity was reduced 160- and 70-fold respectively against ribosomes from Artemia salina. These effects are each approximately 10 times greater than when the residues were previously converted to phenylalanines. Sufficient protein for the Tyr80 to Phe mutant was obtained to carry out an X-ray analysis. Together with mutagenesis data, the structure suggests that the invariance of the two active site Tyr residues is largely caused by structural stability.

Youngsoo Kim

Papers

Site‐directed mutagenesis of ricin A‐chain and implications for the mechanism of action

The 2.0 Å Crystal Structure of Cephalosporin Acylase

Analysis of Several Key Active Site Residues of Ricin A Chain by Mutagenesis and X-ray Crystallography

Crystal structure of PilF: functional implication in the type 4 pilus biogenesis in Pseudomonas aeruginosa

Evidence for a glycosylinositolphospholipid-anchored alkaline phosphatase in the aquatic plant Spirodela oligorrhiza