Novel Biomimetic Human TLR2-Derived Peptides for Potential Targeting of Lipoteichoic Acid: An In Silico Assessment
Antimicrobial resistance is one of the most significant threats to health and economy around the globe and has been compounded by the emergence of COVID-19, raising important consequences for antimicrobial resistance development. Contrary to conventional targeting approaches, the use of biomimetic a...
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doaj-01919c69bd7844b591163bfc345d26c02021-08-26T13:33:21ZengMDPI AGBiomedicines2227-90592021-08-0191063106310.3390/biomedicines9081063Novel Biomimetic Human TLR2-Derived Peptides for Potential Targeting of Lipoteichoic Acid: An In Silico AssessmentNikita Devnarain0Ayman Y. Waddad1Beatriz G. de la Torre2Fernando Albericio3Thirumala Govender4Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South AfricaPeptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South AfricaKRISP, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4001, South AfricaPeptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South AfricaDiscipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South AfricaAntimicrobial resistance is one of the most significant threats to health and economy around the globe and has been compounded by the emergence of COVID-19, raising important consequences for antimicrobial resistance development. Contrary to conventional targeting approaches, the use of biomimetic application via nanoparticles for enhanced cellular targeting, cell penetration and localized antibiotic delivery has been highlighted as a superior approach to identify novel targeting ligands for combatting antimicrobial resistance. Gram-positive bacterial cell walls contain lipoteichoic acid (LTA), which binds specifically to Toll-like receptor 2 (TLR2) on human macrophages. This phenomenon has the potential to be exploited for the design of biomimetic peptides for antibacterial application. In this study, we have derived peptides from sequences present in human TLR2 that bind to LTA with high affinity. In silico approaches including molecular modelling, molecular docking, molecular dynamics, and thermodynamics have enabled the identification of these crucial binding amino acids, the design of four novel biomimetic TLR2-derived peptides and their LTA binding potential. The outcomes of this study have revealed that one of these novel peptides binds to LTA more strongly and stably than the other three peptides and has the potential to enhance LTA targeting and bacterial cell penetration.https://www.mdpi.com/2227-9059/9/8/1063TLR2-derived peptidesbiomimetichuman Toll-like receptor 2lipoteichoic acid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nikita Devnarain Ayman Y. Waddad Beatriz G. de la Torre Fernando Albericio Thirumala Govender |
spellingShingle |
Nikita Devnarain Ayman Y. Waddad Beatriz G. de la Torre Fernando Albericio Thirumala Govender Novel Biomimetic Human TLR2-Derived Peptides for Potential Targeting of Lipoteichoic Acid: An In Silico Assessment Biomedicines TLR2-derived peptides biomimetic human Toll-like receptor 2 lipoteichoic acid |
author_facet |
Nikita Devnarain Ayman Y. Waddad Beatriz G. de la Torre Fernando Albericio Thirumala Govender |
author_sort |
Nikita Devnarain |
title |
Novel Biomimetic Human TLR2-Derived Peptides for Potential Targeting of Lipoteichoic Acid: An In Silico Assessment |
title_short |
Novel Biomimetic Human TLR2-Derived Peptides for Potential Targeting of Lipoteichoic Acid: An In Silico Assessment |
title_full |
Novel Biomimetic Human TLR2-Derived Peptides for Potential Targeting of Lipoteichoic Acid: An In Silico Assessment |
title_fullStr |
Novel Biomimetic Human TLR2-Derived Peptides for Potential Targeting of Lipoteichoic Acid: An In Silico Assessment |
title_full_unstemmed |
Novel Biomimetic Human TLR2-Derived Peptides for Potential Targeting of Lipoteichoic Acid: An In Silico Assessment |
title_sort |
novel biomimetic human tlr2-derived peptides for potential targeting of lipoteichoic acid: an in silico assessment |
publisher |
MDPI AG |
series |
Biomedicines |
issn |
2227-9059 |
publishDate |
2021-08-01 |
description |
Antimicrobial resistance is one of the most significant threats to health and economy around the globe and has been compounded by the emergence of COVID-19, raising important consequences for antimicrobial resistance development. Contrary to conventional targeting approaches, the use of biomimetic application via nanoparticles for enhanced cellular targeting, cell penetration and localized antibiotic delivery has been highlighted as a superior approach to identify novel targeting ligands for combatting antimicrobial resistance. Gram-positive bacterial cell walls contain lipoteichoic acid (LTA), which binds specifically to Toll-like receptor 2 (TLR2) on human macrophages. This phenomenon has the potential to be exploited for the design of biomimetic peptides for antibacterial application. In this study, we have derived peptides from sequences present in human TLR2 that bind to LTA with high affinity. In silico approaches including molecular modelling, molecular docking, molecular dynamics, and thermodynamics have enabled the identification of these crucial binding amino acids, the design of four novel biomimetic TLR2-derived peptides and their LTA binding potential. The outcomes of this study have revealed that one of these novel peptides binds to LTA more strongly and stably than the other three peptides and has the potential to enhance LTA targeting and bacterial cell penetration. |
topic |
TLR2-derived peptides biomimetic human Toll-like receptor 2 lipoteichoic acid |
url |
https://www.mdpi.com/2227-9059/9/8/1063 |
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