David P. Leworthy

Bio: David P. Leworthy is an academic researcher from Royal Dutch Shell. The author has contributed to research in topics: Castanospermum & Castanospermine. The author has an hindex of 5, co-authored 5 publications receiving 777 citations.

Chemical activation of host defence mechanisms as a basis for crop protection

Abstract: THE possibility that a chemical for plant disease control might function by activating the natural resistance mechanisms of the host has been suggested previously1, but there are few well-documented examples. We report here that 2,2-dichloro-3,3-dimethyl cyclopropane carboxylic acid (WL 28325) may exert its systemic fungicidal activity against the rice blast disease (caused by the fungus Piricularia oryzae) in this way.

The dichlorocyclopropanes — Fungicides with an indirect mode of action?

Abstract: The p o s s i b i l i t y that plant diseases can be contro l led by manipulating a p lan t 's own defence mechanisms has been suggested several times in the past (e.g. Day, 1974), but few chemicals which are able to do th is have been descr ibed. 2,2-Dichloro-3,3-dimethylcyclopropane carboxyl ic acid (WL 28325) is a representat ive of a group of compounds, the dichlorocyclopropanes, which are h ighly spec i f i c fo r the r ice lea f ' b l as t ' disease (caused by the fungus P i r i c u l a r i a oryzae). Under cer ta in condit ions WL 28325 inh ib i ted the growth of the pathogen in cu l ture but several aspects of th i s i n h i b i t i o n suggested that th is e f fec t is not re lated to i t s mode of action as a fungic ide. Thus, the i nh i b i t i on was h igh ly dependent on the composition of the growth medium, and, at best, was weak. The a b i l i t y of various dichlorocyclopropanes of s imil a r st ructure to WL 28325 to i n h i b i t growth of P. oryzae in v i t r o did not corre la te with t h e i r a b i l i t y to prevent ' b l as t ' in r i ce . Also, despite the high degree of pathogen s p e c i f i c i t y of WL 28325 as a disease protectant , the compound inh ib i ted the growth of several p lant pathogens in cu l tu re . In addi t ion there was no evidence that WL 28325 was converted wi th in the plant to a der i vat ive with higher i n t r i n s i c f u n g i t o x i c i t y (Langcake and Wickins, 1975a). Certain features of the WL 28325-induced resistance are s im i l a r to those of the natural resistance of r ice to b las t . In both the res is tan t response involves a hypersensi t ive type of browning react ion. Treatment of susceptible r ice plants via the roots with WL 28325 led to enhanced peroxidase a c t i v i t y of the leaves and on subsequent in fec t ion with P. oryzae an accelerated accumulation of brown polymeric material was observed as compared with a comparable in fec t ion of leaves of untreated plants (Langcake and Wickins, 1975b). This brown mater ial is presumed to be a melanin formed by the peroxidasemediated oxidat ion of phenols. Although a role for th is melan inl ike mater ial in l i m i t i n g fungal growth

Systemic acquired resistance

Abstract: This paper examines induced resistance (SAR) in plants against various insect and pathogenic invaders. SAR confers quantitative protection against a broad spectrum of microorganisms in a manner comparable to immunization in mammals, although the underlying mechanisms differ. Discussed here are the molecular events underlying SAR: the mechanisms involved in SAR, including lignification and other structural barriers, pathogenesis-related proteins and their expression, and the signals for SAR including salicylic acid. Recent findings on the biological role of systemin, ethylene, jasmonates, and electrical signals are reviewed. Chemical activators of SAR comprise inorganic compounds, natural compounds, and synthetic compounds. Plants known to exhibit SAR and induced systemic resistance are listed.

Inhibitors of the Biosynthesis and Processing of N-Linked Oligosaccharide Chains

Abstract: A number of glycoproteins have oligosaccharides linked to protein in a GlcNAc----asparagine bond. These oligosaccharides may be either of the complex, the high-mannose or the hybrid structure. Each type of oligosaccharides is initially biosynthesized via lipid-linked oligosaccharides to form a Glc3Man9GlcNAc2-pyrophosphoryl-dolichol and transfer of this oligosaccharide to protein. The oligosaccharide portion is then processed, first of all by removal of all three glucose residues to give a Man9GlcNAc2-protein. This structure may be the immediate precursor to the high-mannose structure or it may be further processed by the removal of a number of mannose residues. Initially four alpha 1,2-linked mannoses are removed to give a Man5 - GlcNAc2 -protein which is then lengthened by the addition of a GlcNAc residue. This new structure, the GlcNAc- Man5 - GlcNAc2 -protein, is the substrate for mannosidase II which removes the alpha 1,3- and alpha 1,6-linked mannoses . Then the other sugars, GlcNAc, galactose, and sialic acid, are added sequentially to give the complex types of glycoproteins. A number of inhibitors have been identified that interfere with glycoprotein biosynthesis, processing, or transport. Some of these inhibitors have been valuable tools to study the reaction pathways while others have been extremely useful for examining the role of carbohydrate in glycoprotein function. For example, tunicamycin and its analogs prevent protein glycosylation by inhibiting the first step in the lipid-linked pathway, i.e., the formation of Glc NAc-pyrophosphoryl-dolichol. These antibiotics have been widely used in a number of functional studies. Another antibiotic that inhibits the lipid-linked saccharide pathway is amphomycin, which blocks the formation of dolichyl-phosphoryl-mannose. In vitro, this antibiotic gives rise to a Man5GlcNAc2 -pyrophosphoryl-dolichol from GDP-[14C]mannose, indicating that the first five mannose residues come directly from GDP-mannose rather than from dolichyl-phosphoryl-mannose. Other antibodies that have been shown to act at the lipid-level are diumycin , tsushimycin , tridecaptin, and flavomycin. In addition to these types of compounds, a number of sugar analogs such as 2-deoxyglucose, fluoroglucose , glucosamine, etc. have been utilized in some interesting experiments. Several compounds have been shown to inhibit glycoprotein processing. One of these, the alkaloid swainsonine , inhibits mannosidase II that removes alpha-1,3 and alpha-1,6 mannose residues from the GlcNAc- Man5GlcNAc2 -peptide. Thus, in cultured cells or in enveloped viruses, swainsonine causes the formation of a hybrid structure.(ABSTRACT TRUNCATED AT 400 WORDS)

Sugar-mimic glycosidase inhibitors: natural occurrence, biological activity and prospects for therapeutic application

Abstract: Alkaloids mimicking the structures of monosaccharides are now believed to be widespread in plants and microorganisms, and these sugar mimics inhibit glycosidases because of a structural resemblance to the sugar moiety of the natural substrate. Naturally occurring sugar mimics with a nitrogen in the ring are classified into five structural classes: polyhydroxylated piperidines, pyrrolidines, indolizidines, pyrrolizidines and nortropanes. Glycosidases are involved in a wide range of important biological processes, such as intestinal digestion, post-translational processing of glycoproteins and the lysosomal catabolism of glycoconjugates. The realization that alkaloidal sugar mimics might have enormous therapeutic potential in many diseases such as viral infection, cancer and diabetes has led to increasing interest and demand for these compounds. Most of these effects can be shown to result from the direct or indirect inhibition of glycosidases. The glycosphingolipid (GSL) storage diseases are relatively rare hereditary disorders that are severe in nature and frequently fatal. Possible strategies for the treatment of these lysosomal storage diseases include enzyme replacement therapy, gene therapy and substrate deprivation. Recently, quite a new therapy for lysosomal storage diseases has been reported, namely a ‘chemical chaperone therapy’ for Fabry disease. In this report, the structural basis for the specificity of inhibition of alkaloidal sugar mimics and their current and potential application to biomedical problems will be reviewed.