Zuchao Ma, PhD, has recently authored a review article titled “Recent advances in chemical synthesis of phosphodiester linkages found in fungal mannans,” published in Carbohydrate Research.
Nearly 100 years of studies have revealed a generalized model of the fungal wall. More recent investigations have revealed that the Candida fungal cell wall is dynamic, adapts to changes in environmental cues, and shapes the host innate immune response.The fungal cell wall structure is primarily composed of a network of chitin, glucan, and mannan. Mannan consist of a backbone, acid-stable chains, and acid-labile chains. Segments of the acid-stable and acid-labile chains are connected with phosphodiester linkages. These linked features are crucial for the immunogenicity of the mannan. A better understanding of these structures will open the door to new treatments, particularly in the realms of Candida vaccines and adjuvants, as well as vaccines for other communicable diseases. This review focuses specifically on the chemical synthesis of these pivotal features in fungal mannans.
Dr. Ma says, “Fungal mannans on the outer cell wall interact with the environment and the human host, shaping immune responses to fungal pathogens. Phosphodiester linkages, which bridge the acid-labile chain within this complex structure, are crucial to its structural and immunological properties. Understanding and synthesizing these linkages is key to developing mannan glycomimetics that may help elicit antifungal immune responses against pathogens like Candida albicans and Candida auris.”
Associate Professor Zuchao Ma directs the Medicinal Chemistry and Drug Discovery Core within the CIIDI. He is joined by additional authors Dr. Harry Ensley, Dr. Douglas Lowman, Dr. Michael Kruppa, and Dr. David L. Williams. Drs. Ma, Ensley, Lowman, and Williams are with Quillen College of Medicine Department of Surgery; Dr. Kruppa is faculty in QCOM Department of Biomedical Sciences. All are members of the Center of Excellence in Inflammation, Infectious Disease, and Immunity (CIIDI).
Above: Representative structure of fungal mannan.
Mannan consist of three basic parts: (1) the α-(1–6)-linked backbone (in black); (2) the acid-stable side chains (in blue); (3) The acid-labile side chains (in red).