Controlled micelle conjugation via charged peptide amphiphiles.

We report the first demonstration of nonionic detergent micelle conjugation and phase separation using purpose-synthesized, peptide amphiphiles, C10 -(Asp)5 and C10 -(Lys)5 . Clustering is achieved in two different ways. Micelles containing the negatively charged peptide amphiphile C10 -(Asp)5 are conjugated (a) via a water-soluble, penta-Lys mediator or (b) to micelles containing the C10 -(Lys)5 peptide amphiphile. Both routes lead to phase separation in the form of oil-rich globules visible in the light microscope. The hydrophobic nature of these regions leads to spontaneous partitioning of hydrophobic dyes into globules that were found to be stable for weeks to months. Extension of the conjugation mechanism to micelles containing a recently discovered, light-driven proton pump King Sejong 1-2 (KS1-2) demonstrates that a membrane protein may be concentrated using peptide amphiphiles while preserving its native conformation as determined by characteristic UV absorption. The potential utility of these peptide amphiphiles for biophysical and biomedical applications is discussed.

Glutathione as a photo-stabilizer of avobenzone: an evaluation under glass-filtered sunlight using UV-spectroscopy.

Avobenzone is the most widely used UVA filter in sunscreen lotion and it is prone to degradation in the presence of sunlight/UV radiation. To overcome the photo-instability of avobenzone, various photostabilizers have been used as additives, including antioxidants such as vitamin C, vitamin E, and ubiquinone. In the present study, the well known antioxidant, glutathione, was evaluated for protecting avobenzone from photodegradation in the presence of glass-filtered sunlight. The features of glutathione as a skin whitener and a radical scavenger in cells have prompted the assessment of the photostabilzing activity of glutathione on avobenzone. Glutathione significantly attenuated the glass-filtered sunlight-induced degradation of avobenzone at equimolar or higher ratios of glutathione and avobenzone. Mutational studies have been undertaken to investigate the role of the thiol group and the isopeptide bond of glutathione on its photoprotection activity towards avobenzone. The thiol group of glutathione plays a vital role in exhibiting the photoprotection activity, which was further supported by the studies on photodegradation of avobonzone in the presence of ß-mercaptoethanol. The dual role of glutathione as a skin whitening agent and a photostabilizer of avobenzone may be useful for the development of multipurpose cosmetic lotions.

Thioacids - synthons for amide bond formation and ligation reactions: assembly of peptides and peptidomimetics.

The synthesis of α-amino thioacids and peptide thioacids and their applications in chemoselective amide bond formation, ligation of peptides/proteins/glycopeptides and synthesis of peptidomimetics are reviewed. A variety of successful methods including both C-terminal and N-terminal activations for the coupling of α-amino thioacids and peptide thioacids have ascertained the thioacid-based protocol as a benign alternative to some of the traditional methods of amide/peptide bond formation which employs carboxyl activation. In addition to the couplings involving unprotected peptide fragments and solid phase synthesis, their use in the synthesis of different classes of peptidomimetics such as thioxopeptides, imide conjugates and acylsulfonamide-peptide conjugates only illustrates the versatility of this functionality in generating diverse classes of molecules, some of which are relevant to drug discovery and chemical biology. A note on more reactive seleno counterparts of thioacids, which can be useful in selective cases, is provided.

Membrane protein crystallization in micelles conjugated by nucleoside base-pairing: A different concept.

The dearth of high quality, three dimensional crystals of membrane proteins, suitable for X-ray diffraction analysis, constitutes a serious barrier to progress in structural biology. To address this challenge, we have developed a new crystallization medium that relies on the conjugation of surfactant micelles via base-pairing of complementary hydrophobic nucleosides. Base-pairs formed at the interface between micelles bring them into proximity with each other; and when the conjugated micelles contain a membrane protein, crystal nucleation centers can be stabilized, thereby promoting crystal growth. Accordingly, two hydrophobic nucleoside derivatives - deoxyguanosine (G) and deoxycytidine (C), each covalently bonded to a 10 carbon chain were synthesized and added to an aqueous solution containing octyl ß-d-thioglucopyranoside micelles. These hydrophobic nucleosides induced the formation of oil-rich globules after 2days incubation at 19°C or after a few hours in the presence of ammonium sulfate; however, phase separation was inhibited by 100mM GMP. The presence of the membrane protein bacteriorhodopsin in the conjugated - micellar dispersion resulted in the growth within the colorless globules of a variety of purple crystals, the color indicating a functional protein. On this basis, we suggest that conjugation of micelles via base-pair complementarity may provide significant assistance to the structural determination of integral membrane proteins.

Catalytic asymmetric reactions and synthesis of quinones.

Asymmetric reactions and the synthesis of various quinones, carried out in the presence of chiral organocatalysts and metal-ligand complexes, are reviewed here. The role of quinones as Michael donors/acceptors, Diels-Alder dienophiles and 1,3-dipolarophiles has been extensively investigated to access complex structural frameworks. Additionally, reports in the literature on the stereoselective synthesis of simple and complex quinoidal compounds with potential biological activities have also been summarized in this review.