Structure-Guided Synthesis of FK506 and FK520 Analogs with Increased Selectivity Exhibit<i>In Vivo</i>Therapeutic Efficacy against Cryptococcus-Reference-Cited by-同舟云学术

Structure-Guided Synthesis of FK506 and FK520 Analogs with Increased Selectivity ExhibitIn VivoTherapeutic Efficacy against Cryptococcus

Published:2022-06-28 Issue:3 Volume:13 Page:
ISSN:2150-7511
Container-title:mBio
language:en
Short-container-title:mBio

Author:

Hoy Michael J.¹^ORCID,Park Eunchong²,Lee Hyunji³,Lim Won Young³,Cole D. Christopher⁴,DeBouver Nicholas D.⁵⁶,Bobay Benjamin G.⁷,Pierce Phillip G.⁵⁶,Fox David⁵⁶,Ciofani Maria²,Juvvadi Praveen R.⁴,Steinbach William⁴,Hong Jiyong³,Heitman Joseph¹

Affiliation:

1. Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA

2. Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA

3. Department of Chemistry, Duke University, Durham, North Carolina, USA

4. Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA

5. UCB Biosciences, Bainbridge Island, Washington, USA

6. Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, Washington, USA

7. Duke University NMR Center, Durham, North Carolina, USA

Abstract

Due to rising rates of antifungal drug resistance and a limited armamentarium of antifungal treatments, there is a paramount need for novel antifungal drugs to treat systemic fungal infections. Calcineurin has been established as an essential and conserved virulence factor in several fungi, making it an attractive antifungal target.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of General Medical Sciences

U.S. Department of Health and Human Services

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Link

https://journals.asm.org/doi/pdf/10.1128/mbio.01049-22

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1. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis