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Uncovering a Hub Signaling Pathway of Antimicrobial-Antifungal-Anticancer Peptides’ Axis on Short Cationic Peptides via Network Pharmacology Study

Short cationic peptides (SCPs) with therapeutic efficacy of antimicrobial peptides (AMPs), antifungal peptides (AFPs), and anticancer peptides (ACPs) are known as an enhancement of the host defense system. Here, we investigated the uppermost peptide(s), hub signaling pathway(s), and their associated...

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Autores principales: Oh, Ki-Kwang, Adnan, Md., Cho, Dong-Ha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875113/
https://www.ncbi.nlm.nih.gov/pubmed/35216171
http://dx.doi.org/10.3390/ijms23042055
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author Oh, Ki-Kwang
Adnan, Md.
Cho, Dong-Ha
author_facet Oh, Ki-Kwang
Adnan, Md.
Cho, Dong-Ha
author_sort Oh, Ki-Kwang
collection PubMed
description Short cationic peptides (SCPs) with therapeutic efficacy of antimicrobial peptides (AMPs), antifungal peptides (AFPs), and anticancer peptides (ACPs) are known as an enhancement of the host defense system. Here, we investigated the uppermost peptide(s), hub signaling pathway(s), and their associated target(s) through network pharmacology. Firstly, we selected SCPs with positive amino acid residues on N- and C- terminals under 500 Dalton via RStudio. Secondly, the overlapping targets between the bacteria-responsive targets (TTD and OMIM) and AMPs’ targets were visualized by VENNY 2.1. Thirdly, the overlapping targets between AFPs’ targets and fungal-responsive targets were exhibited by VENNY 2.1. Fourthly, the overlapping targets between cancer-related targets (TTD and OMIM) and fungal-responsive targets were displayed by VENNY 2.1. Finally, a molecular docking study (MDS) was carried out to discover the most potent peptides on a hub signaling pathway. A total of 1833 SCPs were identified, and AMPs’, AFPs’, and ACPs’ filtration suggested that 197 peptides (30 targets), 81 peptides (6 targets), and 59 peptides (4 targets) were connected, respectively. The AMPs―AFPs―ACPs’ axis indicated that 27 peptides (2 targets) were associated. Each hub signaling pathway for the enhancement of the host defense system was “Inactivation of Rap1 signaling pathway on AMPs”, “Activation of Notch signaling pathway on AMPs―AFPs’ axis”, and “Inactivation of HIF-1 signaling pathway on AMPs―AFPs―ACPs’ axis”. The most potent peptides were assessed via MDS; finally, HPIK on STAT3 and HVTK on NOS2 and on HIF-1 signaling pathway were the most stable complexes. Furthermore, the two peptides had better affinity scores than standard inhibitors (Stattic, 1400 W). Overall, the most potent SCPs for the human defense system were HPIK on STAT3 and HVTK on NOS2, which might inactivate the HIF-1 signaling pathway.
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spelling pubmed-88751132022-02-26 Uncovering a Hub Signaling Pathway of Antimicrobial-Antifungal-Anticancer Peptides’ Axis on Short Cationic Peptides via Network Pharmacology Study Oh, Ki-Kwang Adnan, Md. Cho, Dong-Ha Int J Mol Sci Article Short cationic peptides (SCPs) with therapeutic efficacy of antimicrobial peptides (AMPs), antifungal peptides (AFPs), and anticancer peptides (ACPs) are known as an enhancement of the host defense system. Here, we investigated the uppermost peptide(s), hub signaling pathway(s), and their associated target(s) through network pharmacology. Firstly, we selected SCPs with positive amino acid residues on N- and C- terminals under 500 Dalton via RStudio. Secondly, the overlapping targets between the bacteria-responsive targets (TTD and OMIM) and AMPs’ targets were visualized by VENNY 2.1. Thirdly, the overlapping targets between AFPs’ targets and fungal-responsive targets were exhibited by VENNY 2.1. Fourthly, the overlapping targets between cancer-related targets (TTD and OMIM) and fungal-responsive targets were displayed by VENNY 2.1. Finally, a molecular docking study (MDS) was carried out to discover the most potent peptides on a hub signaling pathway. A total of 1833 SCPs were identified, and AMPs’, AFPs’, and ACPs’ filtration suggested that 197 peptides (30 targets), 81 peptides (6 targets), and 59 peptides (4 targets) were connected, respectively. The AMPs―AFPs―ACPs’ axis indicated that 27 peptides (2 targets) were associated. Each hub signaling pathway for the enhancement of the host defense system was “Inactivation of Rap1 signaling pathway on AMPs”, “Activation of Notch signaling pathway on AMPs―AFPs’ axis”, and “Inactivation of HIF-1 signaling pathway on AMPs―AFPs―ACPs’ axis”. The most potent peptides were assessed via MDS; finally, HPIK on STAT3 and HVTK on NOS2 and on HIF-1 signaling pathway were the most stable complexes. Furthermore, the two peptides had better affinity scores than standard inhibitors (Stattic, 1400 W). Overall, the most potent SCPs for the human defense system were HPIK on STAT3 and HVTK on NOS2, which might inactivate the HIF-1 signaling pathway. MDPI 2022-02-12 /pmc/articles/PMC8875113/ /pubmed/35216171 http://dx.doi.org/10.3390/ijms23042055 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Oh, Ki-Kwang
Adnan, Md.
Cho, Dong-Ha
Uncovering a Hub Signaling Pathway of Antimicrobial-Antifungal-Anticancer Peptides’ Axis on Short Cationic Peptides via Network Pharmacology Study
title Uncovering a Hub Signaling Pathway of Antimicrobial-Antifungal-Anticancer Peptides’ Axis on Short Cationic Peptides via Network Pharmacology Study
title_full Uncovering a Hub Signaling Pathway of Antimicrobial-Antifungal-Anticancer Peptides’ Axis on Short Cationic Peptides via Network Pharmacology Study
title_fullStr Uncovering a Hub Signaling Pathway of Antimicrobial-Antifungal-Anticancer Peptides’ Axis on Short Cationic Peptides via Network Pharmacology Study
title_full_unstemmed Uncovering a Hub Signaling Pathway of Antimicrobial-Antifungal-Anticancer Peptides’ Axis on Short Cationic Peptides via Network Pharmacology Study
title_short Uncovering a Hub Signaling Pathway of Antimicrobial-Antifungal-Anticancer Peptides’ Axis on Short Cationic Peptides via Network Pharmacology Study
title_sort uncovering a hub signaling pathway of antimicrobial-antifungal-anticancer peptides’ axis on short cationic peptides via network pharmacology study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875113/
https://www.ncbi.nlm.nih.gov/pubmed/35216171
http://dx.doi.org/10.3390/ijms23042055
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