As the leading of 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 Glycosylphos-phatidylinositol (GPI) biosynthesis and what can we provide in the area of drug discovery.
Introduction of GPI
GPI is a glycolipid that can be attached to the C-terminus of a protein during posttranslational modification. GPI-anchored proteins are ubiquitously distributed among Eucarya from vertebrates to protozoa and play key roles in a wide variety of biological processes. A diverse range of GPI-anchored proteins has been identified including protozoal surface coat proteins, receptors, adhesion molecules, ectoenzymes, and differentiation antigens. In fungi, GPI-anchored proteins are required for the biosynthesis and integrity of the cell wall. Some GPI-anchored proteins putatively function as glycosylhydrolases, glycosyl-transferases, and peptidases, which may be responsible for cell wall synthesis and remodeling. Thus, disruption of GPI-dependent anchoring would be expected to have suppressing effects on the structure and function of the fungal cell wall and act as the potential targets of antifungals.
Antifungal Drugs Targeting GPI
Gepinacin, an antifungal drug, selectively inhibits Gwt1, a critical acyltransferase required for the biosynthesis of fungal GPI anchors. E1210 is a novel isoxazolyl bis-pyridine wall-active antifungal compound via inhibiting the attachment to the polysaccharide wall component of GPI-dependent anchoring of mannosylated cell wall proteins, thus causing the weakened cell wall and the suppression of fungal growth.
Advantages of GPI as Therapeutic Targets
GPI anchor has been established as a unique mode of protein binding to the plasma membrane. Numerous fungal proteins attach to the cell membrane and/or cell wall via the GPI-dependent pathway. And GPI-anchored proteins are very important for maintaining structure and function of the fungal cell wall. The advantages of antifungals targeting GPI synthesis is as follows.
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 a final result but also provide a whole-process technical support service so that you can keep abreast of the progress of the project and obtain our technical guidance in a timely manner.
If you are interested in our drug target discovery, please contact us for more details or a detailed quote.
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