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Title: Disrupting the Dok3–Card9 interaction with synthetic peptides enhances antifungal effector functions of human neutrophils
Authors: Loh, Jia Tong
Teo, Joey Kay Hui
Kannan, Srinivasaraghavan
Verma, Chandra Shekhar
Lim, Hong-Hwa
Lam, Kong-Peng
Keywords: Science::Biological sciences
Issue Date: 2023
Source: Loh, J. T., Teo, J. K. H., Kannan, S., Verma, C. S., Lim, H. & Lam, K. (2023). Disrupting the Dok3–Card9 interaction with synthetic peptides enhances antifungal effector functions of human neutrophils. Pharmaceutics, 15(7), 1780-.
Project: NMRC/OFIRG19may-0083 
Journal: Pharmaceutics 
Abstract: Invasive fungal disease is an emerging and serious public health threat globally. The expanding population of susceptible individuals, together with the rapid emergence of multidrug-resistant fungi pathogens, call for the development of novel therapeutic strategies beyond the limited repertoire of licensed antifungal drugs. Card9 is a critical signaling molecule involved in antifungal defense; we have previously identified Dok3 to be a key negative regulator of Card9 activity in neutrophils. In this study, we identified two synthetic peptides derived from the coiled-coil domain of Card9, which can specifically block Dok3-Card9 binding. We showed that these peptides are cell-permeable, non-toxic, and can enhance antifungal cytokine production and the phagocytosis of human neutrophils upon fungal infection. Collectively, these data provide a proof of concept that disrupting the Dok3-Card9 interaction can boost the antifungal effector functions of neutrophils; they further suggest the potential utility of these peptide inhibitors as an immune-based therapeutic to fight fungal infection.
ISSN: 1999-4923
DOI: 10.3390/pharmaceutics15071780
Schools: School of Biological Sciences 
Organisations: Bioinformatics Institute, A*STAR 
Department of Biological Sciences, NUS 
Singapore Immunology Network, A*STAR 
Yong Loo Lin School of Medicine, NUS 
Rights: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// 4.0/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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