Enhanced nitric oxide production by macrophages treated with a cell-penetrating peptide conjugate

Arfatur Rahman; Macgregor A. Matthews; Cameron J. Nowell; David K. Chalmers; Philip E. Thompson; Sandra E. Nicholson; Nicholas Barlow; Raymond S. Norton

doi:10.1016/j.bioorg.2022.105763

Enhanced nitric oxide production by macrophages treated with a cell-penetrating peptide conjugate

Arfatur Rahman, Macgregor A. Matthews, Cameron J. Nowell, David K. Chalmers, Philip E. Thompson, Sandra E. Nicholson, Nicholas Barlow, Raymond S. Norton

Research output: Contribution to journal › Article › Research › peer-review

4 Citations (Scopus)

Abstract

The SPRY domain-containing SOCS box protein-2 (SPSB2) plays a critical role in the degradation of inducible nitric oxide synthase (iNOS) in macrophages. In this study, we have conjugated a peptide inhibitor of the iNOS-SPSB2 interaction with a cell-penetrating peptide (CPP) for delivery into macrophages, and confirmed its binding to SPSB2. We have assessed the uptake of a fluorophore-tagged analogue by RAW 264.7 and immortalised bone marrow derived macrophage (iBMDM) cell lines, and shown that the CPP-peptide conjugate enhanced NO production. The findings of this study will be useful in further refinement of CPP-peptide conjugates as leads in the development of new antibiotics that target the host innate immune response.

Original language	English
Article number	105763
Number of pages	9
Journal	Bioorganic Chemistry
Volume	123
DOIs	https://doi.org/10.1016/j.bioorg.2022.105763
Publication status	Published - Jun 2022

Keywords

Cell-penetrating peptide
iNOS
Macrophage
Pathogen killing
SPSB

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@article{20677843341b4351a7f76f311cd5f1ce,

title = "Enhanced nitric oxide production by macrophages treated with a cell-penetrating peptide conjugate",

abstract = "The SPRY domain-containing SOCS box protein-2 (SPSB2) plays a critical role in the degradation of inducible nitric oxide synthase (iNOS) in macrophages. In this study, we have conjugated a peptide inhibitor of the iNOS-SPSB2 interaction with a cell-penetrating peptide (CPP) for delivery into macrophages, and confirmed its binding to SPSB2. We have assessed the uptake of a fluorophore-tagged analogue by RAW 264.7 and immortalised bone marrow derived macrophage (iBMDM) cell lines, and shown that the CPP-peptide conjugate enhanced NO production. The findings of this study will be useful in further refinement of CPP-peptide conjugates as leads in the development of new antibiotics that target the host innate immune response.",

keywords = "Cell-penetrating peptide, iNOS, Macrophage, Pathogen killing, SPSB",

author = "Arfatur Rahman and Matthews, {Macgregor A.} and Nowell, {Cameron J.} and Chalmers, {David K.} and Thompson, {Philip E.} and Nicholson, {Sandra E.} and Nicholas Barlow and Norton, {Raymond S.}",

note = "Funding Information: AR is supported by a co-funded Monash Graduate Scholarship and MAM is supported by an Australian Government Research Training Program (RTP) scholarship. The authors thank Associate Professor James Vince (WEHI) for providing the iBMDM and RAW 264.7 cell lines. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2022",

month = jun,

doi = "10.1016/j.bioorg.2022.105763",

language = "English",

volume = "123",

journal = "Bioorganic Chemistry",

issn = "0045-2068",

publisher = "Elsevier",

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T1 - Enhanced nitric oxide production by macrophages treated with a cell-penetrating peptide conjugate

AU - Rahman, Arfatur

AU - Matthews, Macgregor A.

AU - Nowell, Cameron J.

AU - Chalmers, David K.

AU - Thompson, Philip E.

AU - Nicholson, Sandra E.

AU - Barlow, Nicholas

AU - Norton, Raymond S.

N1 - Funding Information: AR is supported by a co-funded Monash Graduate Scholarship and MAM is supported by an Australian Government Research Training Program (RTP) scholarship. The authors thank Associate Professor James Vince (WEHI) for providing the iBMDM and RAW 264.7 cell lines. Publisher Copyright: © 2022 Elsevier Inc.

PY - 2022/6

Y1 - 2022/6

N2 - The SPRY domain-containing SOCS box protein-2 (SPSB2) plays a critical role in the degradation of inducible nitric oxide synthase (iNOS) in macrophages. In this study, we have conjugated a peptide inhibitor of the iNOS-SPSB2 interaction with a cell-penetrating peptide (CPP) for delivery into macrophages, and confirmed its binding to SPSB2. We have assessed the uptake of a fluorophore-tagged analogue by RAW 264.7 and immortalised bone marrow derived macrophage (iBMDM) cell lines, and shown that the CPP-peptide conjugate enhanced NO production. The findings of this study will be useful in further refinement of CPP-peptide conjugates as leads in the development of new antibiotics that target the host innate immune response.

AB - The SPRY domain-containing SOCS box protein-2 (SPSB2) plays a critical role in the degradation of inducible nitric oxide synthase (iNOS) in macrophages. In this study, we have conjugated a peptide inhibitor of the iNOS-SPSB2 interaction with a cell-penetrating peptide (CPP) for delivery into macrophages, and confirmed its binding to SPSB2. We have assessed the uptake of a fluorophore-tagged analogue by RAW 264.7 and immortalised bone marrow derived macrophage (iBMDM) cell lines, and shown that the CPP-peptide conjugate enhanced NO production. The findings of this study will be useful in further refinement of CPP-peptide conjugates as leads in the development of new antibiotics that target the host innate immune response.

KW - Cell-penetrating peptide

KW - iNOS

KW - Macrophage

KW - Pathogen killing

KW - SPSB

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DO - 10.1016/j.bioorg.2022.105763

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SN - 0045-2068

VL - 123

JO - Bioorganic Chemistry

JF - Bioorganic Chemistry

M1 - 105763

ER -

Enhanced nitric oxide production by macrophages treated with a cell-penetrating peptide conjugate

Abstract

Keywords

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