Molecular and Cellular Aspects of Chitin Synthesis in Larval Artemia

Horst, Michael N.

doi:10.1007/978-1-4757-0004-6_7

Cited by 7 publications

(1 citation statement)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was described that chitin synthesized in vitro by preparations from M. rouxii contained a short polypeptide covalently-bound to the reducing end of the polysaccharide [27,28]. In brine shrimp it was described that GlcNAc bound to dolichol was transferred to a protein acceptor in a second reaction [29,30]. Merz et al [11] obtained evidence that chitin biosynthesis occurred in two steps with the involvement of a protein acceptor.…”

Section: Reaction Mechanismmentioning

confidence: 98%

Chitin Synthesis as a Target for Antifungal Drugs

Ruiz-Herrera¹,

San-Blas

2003

CDTID

View full text Add to dashboard Cite

Human mycoses have become a threat to health world-wide. Unfortunately there are only a limited number of antimycotic drugs in use. Promising targets for drugs specific against fungi are those affecting chitin synthesis. Chitin is absent in vertebrates, and is essential for fungal wall integrity. A thorough knowledge of the mechanism of chitin synthesis is required to design specific inhibitors. We review here our current understanding of the process, and the most promising drugs that inhibit it. Chitin is made by chitin synthases requiring specific microvesicles, the chitosomes, for intracellular transport. Fungi contain several chitin synthases, some of which may be essential at a certain stage. This phenomenon is important to take into account for drug design. The most widely studied chitin synthase inhibitors are polyoxins and nikkomycins that probably bind to the catalytic site of chitin synthases. These are not equally susceptible to the drugs. In Saccharomyces cerevisiae the order of sensitivity is: Chs3p>Chs1p>Chs2p. Main problems for their succesful use in vivo are: low permeability, and different susceptibility of fungal species, and variable responses in animal models. Chemical modifications have been proposed to make more potent derivatives. Other synthetic or natural compounds are also promising as possible inhibitors, but their properties are less well known. Rational drug design has proceeded only on the basis of existing inhibitors, because the structure of the active site of chitin synthase is unknown. Undoubtedly, determination of this, and the biosynthetic mechanism will reveal unexpected drug targets in the future.

show abstract

Section: Reaction Mechanismmentioning

confidence: 98%

Chitin Synthesis as a Target for Antifungal Drugs

Ruiz-Herrera¹,

San-Blas

2003

CDTID

View full text Add to dashboard Cite

show abstract

Review: Approaches to New Parasiticides

Londershausen

1996

Pestic. Sci.

140

View full text Add to dashboard Cite

Intensive use of parasiticides has sometimes led to severe resistance in arthropods and helminths of veterinary importance. In the context of the growing awareness of parasitic diseases, this has created a public demand for effective and safe control agents. During the last two decades considerable knowledge in parasite neurophysiology and endocrinology has accumulated which allows the development of new screening procedures and target‐site‐directed approaches for the discovery of new drugs. The suitability of this strategic approach is discussed on the basis of recent discoveries of new chemical and natural compounds. In particular, target sites such as GABAA receptors, muscarinic and nicotinic acetylcholine receptors, cuticle synthesis and degradation, ecdysteroid receptors, the calcium release channel and semiochemicals have been selected in order to demonstrate the current approaches to identify new chemical entities, biologically active against nematodes and arthropods.

show abstract

Dolichol phosphorylation occurs via a CTP‐dependent reaction in Artemia larvae

Horst

1989

J. Exp. Zool.

View full text Add to dashboard Cite

The phosphorylation of dolichol in larval stages of the brine shrimp, Artemia salina, has been investigated. The dolichol kinase has been assayed in crude microsomes; the enzyme requires CTP as phosphoryl donor and calcium as divalent cation. Activity increases with both incubation time and added microsomal protein. The product of the reaction has been characterized by chromatographic and enzymatic procedures. With gamma-32P CTP as substrate, the apparent Km for CTP is 24 microM. Enzymatic activity is stimulated fivefold by exogenous dolichol. The specific activity of the enzyme increases with the frequency of molting. Dolichol kinase activity was detectable in membranes prepared from dormant Artemia cysts. The low level in dormancy may anticipate the critical role of the enzyme during hatching.

show abstract

Molecular and Cellular Aspects of Chitin Synthesis in Larval Artemia

Cited by 7 publications

References 22 publications

Chitin Synthesis as a Target for Antifungal Drugs

Chitin Synthesis as a Target for Antifungal Drugs

Review: Approaches to New Parasiticides

Dolichol phosphorylation occurs via a CTP‐dependent reaction in Artemia larvae

Contact Info

Product

Resources

About