Proteins catalyze specific chemical reactions and carry out highly selective molecular recognition because they adopt well-defined three-dimensional structures and position chemically reactive functional groups in specific constellations. Proteins attain these well-defined structures through the complex process of protein folding. We seek to emulate these protein functions by constructing macromolecules that are easier to engineer by avoiding folding altogether. Toward that goal, we have developed an approach for the synthesis of macromolecules with programmable shapes. As described in this Account, we have constructed synthetic building blocks called bis-amino acids that we then couple through pairs of amide bonds to create water-soluble, spiroladder oligomers (bis-peptides) with well-defined three-dimensional structures. Bis-peptides use the conformational preferences of fused rings, stereochemistry, and strong covalent bonds to define their shape, unlike natural proteins and synthetic foldamers, which depend on noncovalent interactions and an unpredictable folding process to attain structure. Using these bis-amino acid monomers, we have built and characterized a number of bis-peptide nanostructures. We also constructed a molecular actuator that undergoes a large change in conformation under the control of metal exchange; the first application of bis-peptides. We are currently developing further approaches to functionalize bis-peptides as scaffolds to present well-defined constellations of functional groups. Such macromolecules could facilitate multifunctional catalysis and molecular recognition and lead to nanoscale molecular devices.
The mechanism of testicular toxicity of lead (Pb) and cadmium (Cd) is poorly understood. Previous studies focused on single metal-related changes in testicular toxicity. This study points towards the possible involvement of Pb- and Cd-induced oxidative stress in the suppression of steroidogenesis. The oxidative status of testis of adult male rats exposed to Pb acetate and cadmium acetate either alone or in combination at a dose of 0.025 mg kg(-1) body weight of metal intraperitoneally for 15 days was studied. Pb and Cd caused an increase in reactive oxygen species (ROS) by elevating testicular malondialdehydes (MDA) and decrease in activities of testicular antioxidant enzymes superoxide dismutase (SOD), catalase, glucose 6 phosphate dehydrogenase (G6PDH) and glutathione-S-transferase (GST) in mitochondrial and/or post-mitochondrial fraction. Activities of steroidogenic enzymes 3β and 17β-hydroxysteroid dehydrogenase also decreased significantly leading to altered testosterone production. Metal-exposed groups showed significantly decreased testicular and epididymal sperm count. Epididymal sperm motility and viability was also decreased on Pb and Cd exposure. Cd exposure showed more toxic effect than lead exposure, while combined exposure demonstrated least toxicity. In vitro experiments showed that vitamin C restores steroidogenic enzyme activities, suggesting that Pb- and Cd-induced ROS inhibits the testicular steroidogenesis.
We demonstrate PolyAla synthesis using 5% piperazine + 2% DBU, which significantly reduces deletion products arising due to incomplete Fmoc-deprotection and can be used for deletion-free assembly of aggregation prone difficult peptides.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.