Synthesis of the fungal metabolite YWA1 and related constructs as tools to study MelLec-mediated immune response to Aspergillus infections

Monica Piras; Ilaria Patruno; Christina Nikolakopoulou; Janet A Willment; Nikki  Sloan; Chiara Zanato; Gordon Brown; Matteo  Zanda

doi:10.1021/acs.joc.0c02324

Synthesis of the fungal metabolite YWA1 and related constructs as tools to study MelLec-mediated immune response to Aspergillus infections

Monica Piras, Ilaria Patruno, Christina Nikolakopoulou, Janet A Willment, Nikki Sloan, Chiara Zanato, Gordon Brown^* (Corresponding Author), Matteo Zanda^* (Corresponding Author)

^*Corresponding author for this work

Applied Medicine

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Abstract

We describe the chemical synthesis of the fungal naphthopyrones YWA1 and fonsecin B, as well as their functionalization with an amine-spacer arm and the conjugation of the resulting molecules to three different functional tags (i.e. biotin, Oregon green, PyMPO). The naphthopyrone-biotin and -PyMPO constructs maintained the ability to bind the Ctype lectin receptor MelLec, whose interaction with immunologically active fungal metabolites (i.e. DHN-melanin and YWA1) is a key step in host recognition and induction of protective immune responses against A. fumigatus. The fluorescent Fonsecin B-PyMPO construct 21 was used to selectively visualize MelLec-expressing cells, thus validating the potential of this strategy for studying the role and functions of MelLec in immunity.

Original language	English
Pages (from-to)	6044-6055
Number of pages	12
Journal	Journal of Organic Chemistry
Volume	86
Issue number	9
Early online date	22 Apr 2021
DOIs	https://doi.org/10.1021/acs.joc.0c02324
Publication status	Published - 7 May 2021

Bibliographical note

Funding Sources
Funding was provided by the Wellcome Trust (102705, 097377), the Medical Research Council Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).
ACKNOWLEDGMENT
We thank Ian Fraser Flow Cytometry and Microscopy and Histology facilities, University of Aberdeen.

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Cite this

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title = "Synthesis of the fungal metabolite YWA1 and related constructs as tools to study MelLec-mediated immune response to Aspergillus infections",

abstract = "We describe the chemical synthesis of the fungal naphthopyrones YWA1 and fonsecin B, as well as their functionalization with an amine-spacer arm and the conjugation of the resulting molecules to three different functional tags (i.e. biotin, Oregon green, PyMPO). The naphthopyrone-biotin and -PyMPO constructs maintained the ability to bind the Ctype lectin receptor MelLec, whose interaction with immunologically active fungal metabolites (i.e. DHN-melanin and YWA1) is a key step in host recognition and induction of protective immune responses against A. fumigatus. The fluorescent Fonsecin B-PyMPO construct 21 was used to selectively visualize MelLec-expressing cells, thus validating the potential of this strategy for studying the role and functions of MelLec in immunity.",

author = "Monica Piras and Ilaria Patruno and Christina Nikolakopoulou and Willment, {Janet A} and Nikki Sloan and Chiara Zanato and Gordon Brown and Matteo Zanda",

note = "Funding Sources Funding was provided by the Wellcome Trust (102705, 097377), the Medical Research Council Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1). ACKNOWLEDGMENT We thank Ian Fraser Flow Cytometry and Microscopy and Histology facilities, University of Aberdeen.",

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doi = "10.1021/acs.joc.0c02324",

language = "English",

volume = "86",

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journal = "Journal of Organic Chemistry",

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publisher = "American Chemical Society",

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T1 - Synthesis of the fungal metabolite YWA1 and related constructs as tools to study MelLec-mediated immune response to Aspergillus infections

AU - Piras, Monica

AU - Patruno, Ilaria

AU - Nikolakopoulou, Christina

AU - Willment, Janet A

AU - Sloan, Nikki

AU - Zanato, Chiara

AU - Brown, Gordon

AU - Zanda, Matteo

N1 - Funding Sources Funding was provided by the Wellcome Trust (102705, 097377), the Medical Research Council Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1). ACKNOWLEDGMENT We thank Ian Fraser Flow Cytometry and Microscopy and Histology facilities, University of Aberdeen.

PY - 2021/5/7

Y1 - 2021/5/7

N2 - We describe the chemical synthesis of the fungal naphthopyrones YWA1 and fonsecin B, as well as their functionalization with an amine-spacer arm and the conjugation of the resulting molecules to three different functional tags (i.e. biotin, Oregon green, PyMPO). The naphthopyrone-biotin and -PyMPO constructs maintained the ability to bind the Ctype lectin receptor MelLec, whose interaction with immunologically active fungal metabolites (i.e. DHN-melanin and YWA1) is a key step in host recognition and induction of protective immune responses against A. fumigatus. The fluorescent Fonsecin B-PyMPO construct 21 was used to selectively visualize MelLec-expressing cells, thus validating the potential of this strategy for studying the role and functions of MelLec in immunity.

AB - We describe the chemical synthesis of the fungal naphthopyrones YWA1 and fonsecin B, as well as their functionalization with an amine-spacer arm and the conjugation of the resulting molecules to three different functional tags (i.e. biotin, Oregon green, PyMPO). The naphthopyrone-biotin and -PyMPO constructs maintained the ability to bind the Ctype lectin receptor MelLec, whose interaction with immunologically active fungal metabolites (i.e. DHN-melanin and YWA1) is a key step in host recognition and induction of protective immune responses against A. fumigatus. The fluorescent Fonsecin B-PyMPO construct 21 was used to selectively visualize MelLec-expressing cells, thus validating the potential of this strategy for studying the role and functions of MelLec in immunity.

U2 - 10.1021/acs.joc.0c02324

DO - 10.1021/acs.joc.0c02324

M3 - Article

SN - 0022-3263

VL - 86

SP - 6044

EP - 6055

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 9

ER -

Synthesis of the fungal metabolite YWA1 and related constructs as tools to study MelLec-mediated immune response to Aspergillus infections

Abstract

Bibliographical note

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Microscopy and Histology

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