Chemical Cleavage of Peptide Bonds
Roger L. Lundblad in Chemical Reagents for Protein Modification, 2020
The elucidation of the covalent structure of a protein requires the development of specific, reproducible methods for cleavage of the protein into fragments of a size amenable to structural analysis. Proteolytic enzymes such as trypsin, chymotrypsin, and pepsin have proved quite useful in the cleavage of specific peptide bonds in proteins. Partial acid hydrolysis is the oldest of the various chemical approaches to the cleavage of specific peptide bonds. The cleavage of protein at asparaginyl-glycyl peptide bonds with has proved useful in selected circumstances. Cleavage of methionine-containing peptide bonds with cyanogen bromide is certainly the most widely used method for specific chemical cleavage of peptide bonds. The reaction mixture was then neutralized with acetic acid and excess peroxide removed with catalase. Alternatively, cleavage can be accomplished with bromide or performic acid. The yield of cleavage is measured either by the loss of methionine or by the sum of homoserine and homoserine lactone after acid hydrolysis.
Terpenes
Andrew Pengelly, Kerry Bone in The Constituents of Medicinal Plants, 2020
Terpenoids, or terpenes, comprise one of the most important groups of active compounds in plants with over 20000 known structures. The bitter iridoid monoterpenes usually occur as glycosides. Non-glycosidic iridoids include the sedative valepotriates found in valerian— Valeriana spp. Numerous sesquiterpene lactone-containing plants of the Asteraceae family are known to cause contact dermatitis in humans. In one case a patient developed acute dermatitis of the right hand with severe blistering following a single application of Arnica tincture. The term ‘bitter principle’ is used in reference to any one of a group of unrelated constituents responsible for the bitter taste characteristic of many herbs. Most are derived from terpenes, though non-terpene structures such as certain flavonoids and alkaloids are included with the bitters. The main group of interest is the carotenoids, over 600 of which are found in nature—providing red, orange and yellow pigments to fruits and vegetables.
Bioactive and Functional Oligomers Derived from Natural PHA and Their Synthetic Analogs
Martin Koller in The Handbook of Polyhydroxyalkanoates, 2020
Polyhydroxyalkanoate oligomers (oligo-PHA) are low molar mass PHA consisting of a small number of 3-hydroxyacid repeat units (usually not more than 200 residue units). They can be synthesized either naturally in eukaryotic cells and in prokaryotic cells through intracellular or extracellular degradation of storage PHA to yield natural oligomers, or via several chemical modifications such as basic hydrolysis or transesterification. The synthetic analogs of natural PHA oligomers are obtained by anionic ring-opening polymerization (ROP) of β-substituted β-lactones. These synthetic and biodegradable oligomers, through various chemical modifications, can further allow the preparation of bioactive oligomers with attractive properties for novel and high value-added applications, especially in medicine, agrochemistry, and cosmetology. Bioactive oligomers are also biodegradable: they possess enhanced properties, controlled functional end groups, and thus can be potential components of copolymers or blends with other biodegradable polymers. The natural and synthetic routes used for the preparation of selected bioactive PHA oligomers and their detailed characterization by mass spectrometry are discussed in this chapter.
Recent advances in the discovery and development of stilbenes and lactones in anticancer therapy
Published in Expert Opinion on Therapeutic Patents, 2004
Salmaan H Inayat-Hussain, Noel F Thomas
The stilbene and lactone moieties are important components of a number of compounds that have potential therapeutic roles in many areas including anticancer therapy. Since the significance of these moieties were recognised, a myriad of structurally-related or different analogues have been studied and tested against various pharmacological modalities that may provide novel targets in therapies, for example in conditions where insufficient apoptosis leads to the formation of cancer. Recently, there have been a number of studies directed at the search for novel anticancer compounds incorporating stilbene and/or lactone moieties. The particular aim of this review is to focus on, and summarise, selected patents from 1999 – 2003 on stilbenes and lactones with anticancer properties.
Dehydrocostus Lactone Enhances Tumor Necrosis Factor‐α‐Induced Apoptosis of Human Leukemia HL‐60 Cells
Published in Immunopharmacology and Immunotoxicology, 2004
G. S. Oh, H. O. Pae, H. T. Chung, J. W. Kwon, J. H. Lee, T. O. Kwon, S. Y. Kwon, B. H. Chon, Young Gab Yun
Sesquiterpene lactones have raised considerable interest because of their ability to block the activation of nuclear transcription factor‐κB (NF‐κB). NF‐κB plays an important role in the resistance of cancer cells to the induction of apoptosis by anticancer drugs and tumor necrosis factor‐α (TNF‐α). Pharmacological inhibition of NF‐κB offers the promise of enhancing the efficacy of anticancer therapies. Here, we demonstrate that dehydrocostus lactone (DL), the major sesquiterpene lactone isolated from the roots of Saussurea lappa, inhibits NF‐κB activation by preventing TNF‐α‐induced degradation and phosphorylation of its inhibitory protein I‐κBα in human leukemia HL‐60 cells and that DL renders HL‐60 cells susceptible to TNF‐α‐induced apoptosis by enhancing caspase‐8 and caspase‐3 activities.
Ascorbic Acid Levels and Neutrophil Superoxide Production in Blood of Pre-, Early and Late Hypertensive Stroke-Prone Spontaneously Hypertensive Rats
Published in Clinical and Experimental Hypertension, 2011
Yoko Sato, Masahiko Ikeda, Tomohiro Ito, Takako Tomita, Kaori Yokotani, Masatsune Murata, Keizo Umegaki
We compared ascorbic acid (AA) levels in the blood and TPA- and fMLP-stimulated superoxide (O2•−) production in neutrophils of pre-, early, and late hypertensive stroke-prone spontaneously hypertensive rats (SHRSP) with those of age-matched Wistar Kyoto rats (WKY), or two other normotensive strains of rats. Plasma and lymphocyte AA levels were about two-fold higher in SHRSP as early as 4 weeks old compared to WKY, and also higher than those of Wistar and Sprague-Dawley (SD) rats. Levels of AA were high in the liver and adrenal glands of SHRSP, indicating congenitally high AA levels. The production of O2•− in neutrophils was about two-fold higher in SHRSP than in WKY even at 4 weeks of age, and increased with age in both strains. Among SHRSP, AA levels in lymphocytes decreased at the late hypertensive stages with a decrease in hepatic l-gulono-γ-lactone oxidase (GLO) activities. These data suggest that bi-phasic AA levels in the blood of SHRSP comprise congenitally high levels and a decrease after persistent hypertension due to enhanced O2•− production and a decrease in de novo AA synthesis through GLO.