Peptide and protein biological activities depend on their three dimensionals structures in the free state and when interacting with their receptors/acceptors. The backbone conformations such as α‐helix, β‐sheet, β‐turn, and so forth provide critical templates for the three‐dimensional structure, but the overall shape and intrinsic stereoelectronic properties of the peptide or protein important for molecular recognition, signal transduction, enzymatic specificity, immunomodulation, and other biological effects depend on arrangement of the side chain groups in three‐dimensional chi space (their χ1, χ2, etc. torsional angles) In this paper we explore approaches to the de novo design of polypeptides and peptidomimetics with biased or specific conformational/topographical properties in chi space. We consider computational and experimental methods that can be used to examine the effects of specific structural modifications in constraining side chain groups of amino acid residues and their similarities in chi space to the natural amino acids to evaluate what sort of mimetics are likely to minic normal amino acids. We then examine some of the asymmetric synthetic methods that are being developed to obtain the amino acid mimetics. Finally, we consider selected examples in the literature where these specialized amino acids have been incorporated in biologically active peptides and the specific insights they have provided regarding the topographical requirements for bioactive peptide potency, selectivity, and other biochemical and pharmacological properties. Constraints in chi space show great promise as useful tools in peptide, protein, and peptidomimetic de novo design of structures and pharmacophores with specific stereostructural, biochemical and biological properties. © 1997 John Wiley & Sons, Inc. Biopoly 43: 219–266, 1997

The o f tlir diol of ally1 tosylate ( Catalytic Asymmetric Aminohydroxylation (AA) of Olefins""Guigen Li, Han-Ting Chang, and K. Barry Sharpless* Deciiccrrcd to the niemory of F6li.y SerratosuThe /&hydroxyamino group is frequently found in biologically active molecules. We report here that this important unit can now be synthesized directly from olefins in enantiomerically enriched form. The new osmium-catalyzed asymmetric process is exemplified by the synthesis of the enantiomers of the taxol side chain (2 and en/-2) from methyl cinnamate (1) (Scheme 1).

The pathogenic bacterium Pseudomonas aeruginosa utilizes the 3-oxododecanoyl homoserine lactone (3OC 12 -HSL) autoinducer as a signaling molecule to coordinate the expression of virulence genes through quorum sensing. 3OC 12 -HSL also affects responses in host cells, including the upregulation of genes encoding inflammatory cytokines. This proinflammatory response may exacerbate underlying disease during P. aeruginosa infections. The specific mechanism(s) through which 3OC 12 -HSL influences host responses is unclear, and no mammalian receptors for 3OC 12 -HSL have been identified to date. Here, we report that 3OC 12 -HSL increases mRNA levels for a common panel of proinflammatory genes in murine fibroblasts and human lung epithelial cells. To identify putative 3OC 12 -HSL receptors, we examined the expression patterns of a panel of nuclear hormone receptors in these two cell lines and determined that both peroxisome proliferator-activated receptor beta/delta (PPAR␤/␦) and PPAR␥ were expressed. 3OC 12 -HSL functioned as an agonist of PPAR␤/␦ transcriptional activity and an antagonist of PPAR␥ transcriptional activity and inhibited the DNA binding ability of PPAR␥. The proinflammatory effect of 3OC 12 -HSL in lung epithelial cells was blocked by the PPAR␥ agonist rosiglitazone, suggesting that 3OC 12 -HSL and rosiglitazone are mutually antagonistic negative and positive regulators of PPAR␥ activity, respectively. These data identify PPAR␤/␦ and PPAR␥ as putative mammalian 3OC 12 -HSL receptors and suggest that PPAR␥ agonists may be employed as anti-inflammatory therapeutics for P. aeruginosa infections.

The utilization of redox-active organic species in aqueous redox flow batteries holds great promise for large-scale and sustainable energy storage. Herein, we report the low-temperature green synthesis of three different phenazine derivatives and investigate their performances in alkaline organic redox flow batteries. Electrochemical characterizations reveal that the ortho-substituents of the hydroxyl groups in phenazine derivatives have significant influences on the battery performances. By introducing an additional phenyl group adjacent to the hydroxyl group in the phenazine motif and a carboxyl group with strong solubilizing effect, the redox flow battery based on fused-ring benzo­[a]­hydroxyphenazine-7/8-carboxylic acid with 1.0 M electron concentration exhibits greatly improved capacity retention rate of 99.986% cycle–1 (99.92% day–1) and stable average energy efficiency of ∼80% for over 1300 cycles. Moreover, a combinatorial library of hydroxyphenazine derivatives with varying substituent groups was built, and their redox properties were simulated to guide further molecular structure design of phenazine-derived electroactive compounds.

Aqueous redox flow batteries (ARFBs) based on the electrolyte solutions of redox-active organic molecules are very attractive for the application of large-scale electrochemical energy storage. We propose a high-performance ARFB system utilizing 2hydroxy-3-carboxy-1,4-naphthoquinone (2,3-HCNQ) and K 4 Fe-(CN) 6 as the anolyte and catholyte active species, respectively. The 2,3-HCNQ molecule exhibits high solubility and can carry out a reversible two-electron redox process with rapid redox kinetics. The assembled 2,3-HCNQ/K 4 Fe(CN) 6 ARFB delivered a cell voltage of 1.02 V and realized a peak power density of 0.255 W cm −2 . The 2,3-HCNQ/K 4 Fe(CN) 6 ARFB can be stably operated at a current density of 100 mA cm −2 for long-term cycling (with a capacity retention of ∼94.7% after 100 cycles).