With years of experiences in drug discovery, Creative Biolabs is devoted to helping global clients to explore and identify the potential and well-recognized targets for antifungal drug development. Here we describe the attractive antifungal targets involved in the glucan biosynthesis.
Introduction of Glucan
Glucan is the most abundant polysaccharide of the fungal cell wall and its dry weight approximately accounts for 50-60% of the wall by dry weight. Thus, glucan biosynthesis provides an attractive target for the development of antifungal drugs. In general, between 65% and 90% of the cell wall glucan is found to be beta-1,3-glucan, but other glucans, such as beta-1,6-, mixed beta-1,3- and beta-1,4-, alpha-1,3-, and alpha-1,4-linked glucans, have been found in various fungal cell walls. Glucans are polymers composed of repeating glucose residues that are assembled into chains through a variety of chemical linkages. Synthesis of the polymer made up of beta1,3 chains with a variable degree of beta1,6 branching involves several reactions: initiation, chain elongation, and branching. In the elongation step, glucan synthetases exert an important role via catalyzing glucan synthesis.
Glucan Synthases
Studies have revealed a (1,3)-β-glucan synthase complex that consists of a catalytic subunit encoded by the FKS1 and FKS2 genes and a regulatory subunit encoded by the RHO1 gene. The (1,3)-β-glucan synthases function as the key regulator for (1,3)-β-glucan synthesis. Echinocandins, the inhibitor of catalytic subunit of (1,3)-β-D-glucan synthase, are the first antifungals to target the fungal cell wall. In addition, although the β-1,6-glucan synthase has yet to be definitively identified in any fungal species, a number of proteins related to the synthesis of β-1,6-glucan have been identified in S. cerevisiae including the KRE5, BIG1, and ROT1 proteins, which have been localized to the ER and function in the quality control/protein-folding activities. Therefore, these proteins may also act as the potential targets of antifungal drugs.
Fig.1 Glucan synthase acts as the antifungals target. (Desoubeauxio, 2010)
Advantages of Glucan Biosynthesis as Therapeutic Targets
As the major components of the fungal cell wall, many antifungal drugs are developed to target the glucan synthesis, especially the (1,3)-β-glucan synthase. Glucan synthesis acts as the target of antifungal drugs meet with many characteristics of drug targets. The followings are potential advantages.
What Can We Provide?
Creative Biolabs has an outstanding professional team and diverse advanced technology platforms to provide customers worldwide with a full range of antifungal drug discovery services including target identification and validation, Hit identification, Hit to lead, Lead optimization, and IND enabling. Our services not only enable you to obtain final results but also provide whole-process technical support services so that you can keep abreast of the progress of the project and obtain our technical guidance in a timely manner.
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Reference
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