Chitin synthesis inhibitors: old molecules and new developments

Abstract Chitin is the most abundant natural aminopolysaccharide and serves as a structural component of extracellular matrices. It is found in fungal septa, spores, and cell walls, and in arthropod cuticles and peritrophic matrices, squid pens, mollusk shells, nematode egg shells, and some protozoan cyst walls. As prokaryotes, plants and vertebrates including humans do not produce chitin, its synthesis is considered as an attractive target site for fungicides, insecticides, and acaricides. Although no chitin synthesis inhibitor has been developed into a therapeutic drug to treat fungal infections in humans, a larger number of compounds have been successfully launched worldwide to combat arthropod pests in agriculture and forestry. This review summarizes the latest advances on the mode of action of chitin synthesis inhibitors with a special focus on those molecules that act on a postcatalytic step of chitin synthesis.     

Recent developments

Law Section

Recent developments     

Glycogen and its metabolism: some new developments and old themes

Glycogen is a branched polymer of glucose that acts as a store of energy in times of nutritional sufficiency for utilization in times of need. Its metabolism has been the subject of extensive investigation and much is known about its regulation by hormones such as insulin, glucagon and adrenaline (epinephrine). There has been debate over the relative importance of allosteric compared with covalent control of the key biosynthetic enzyme, glycogen synthase, as well as the relative importance of glucose entry into cells compared with glycogen synthase regulation in determining glycogen accumulation. Significant new developments in eukaryotic glycogen metabolism over the last decade or so include: (i) three-dimensional structures of the biosynthetic enzymes glycogenin and glycogen synthase, with associated implications for mechanism and control; (ii) analyses of several genetically engineered mice with altered glycogen metabolism that shed light on the mechanism of control; (iii) greater appreciation of the spatial aspects of glycogen metabolism, including more focus on the lysosomal degradation of glycogen; and (iv) glycogen phosphorylation and advances in the study of Lafora disease, which is emerging as a glycogen storage disease.     

The repair of DNA damage: Recent developments and new insights

This brief review presents the salient features of new developments in the enzymatic repair of base damage to DNA. DNA glycosylases and apurinic/ apyrimidinic (AP) endonucleases are reviewed and evidence is presented that in at least two prokaryote systems incision of UV-irradiated DNA occurs by the sequential action of these two classes of enzymes. In contradistinction, the uvrA, uvrB, and uvrC gene products of E coli appear to function as a multiprotein complex that catalyzes hydrolysis of phosphodiester bonds in damaged DNA directly. The inducible rapid repair of O⁶- methylguanine in E coli is also reviewed.     

Recent developments in cancer vaccines

The adoptive transfer of cancer Ag-specific effector T cells in patients can result in tumor rejection, thereby illustrating the immune system potential for cancer therapy. Ideally, one would like to directly induce efficient tumor-specific effector and memory T cells through vaccination. Therapeutic vaccines have two objectives: priming Ag-specific T cells and reprogramming memory T cells (i.e., a transformation from one type of immunity to another, for example, regulatory to cytotoxic). Recent successful phase III clinical trials showing benefit to the patients revived cancer vaccines. Dendritic cells (DCs) are essential in generation of immune responses, and as such represent targets and vectors for vaccination. We have learned that different DC subsets elicit different T cells. Similarly, different activation methods result in DCs able to elicit distinct T cells. We contend that a careful manipulation of activated DCs will allow cancer immunotherapists to produce the next generation of highly efficient cancer vaccines.     

Recent developments in regenerative ophthalmology

Regenerative medicine(RM) is one of the most promising disciplines for advancements in modern medicine, and regenerative ophthalmology(RO) is one of the most active fields of regenerative medicine. This review aims to provide an overview of regenerative ophthalmology, including the range of tools and materials being used, and to describe its application in ophthalmologic subspecialties, with the exception of surgical implantation of artificial tissues or organs(e.g., contact lens, artificial cornea, intraocular lens, artificial retina, and bionic eyes) due to space limitations. In addition, current challenges and limitations of regenerative ophthalmology are discussed and future directions are highlighted.     

Recent developments in enediyne chemistry

The enediynes are known for highly potent anticancer, antimicrobial, as well as cytotoxic activities. The discovery of enediynes from natural sources was achieved in late 1980s. They are presently of high interest, because they exert their biological action due to their ability to form a diradical, which abstracts H-atoms from the DNA backbone, thus causing cell death. Nowadays, the major works are dedicated to the syntheses of enediynes. This review covers recent developments in enediyne chemistry of the last few decades. It is subdivided in six chapters dealing with the discussion of the chemistry and biological significances of enediynes, and the factors responsible for a better activation of enediynes and potent biological evaluations.