1,3,5-Triazine as Branching Connector for the Construction of Novel Antimicrobial Peptide Dendrimers: Synthesis and Biological Characterization

Author:

Sheyi Rotimi1,Mhlongo Jessica T.12,Jorba Marta3ORCID,Fusté Ester34ORCID,Sharma Anamika12ORCID,Viñas Miguel3ORCID,Albericio Fernando15ORCID,Espinal Paula3ORCID,de la Torre Beatriz G.2ORCID

Affiliation:

1. Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, KwaZulu-Natal, South Africa

2. School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4041, KwaZulu-Natal, South Africa

3. Laboratory of Molecular Microbiology & Antimicrobials, Department of Pathology and Experimental Therapeutics, Faculty of Medicine & Health Sciences, IDIBELL—University of Barcelona, Campus Bellvitge, 08907 L’Hospitalet de Llobregat, Barcelona, Spain

4. Department of Public Health, Mental Health and Maternal and Child Health Nursing, University of Barcelona, Campus Bellvitge, 08907 L’Hospitalet de Llobregat, Barcelona, Spain

5. Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Department of Organic Chemistry, University of Barcelona, Martí i Franqués 1-11, 08028 Barcelona, Barcelona, Spain

Abstract

Peptides displaying antimicrobial properties are being regarded as useful tools to evade and combat antimicrobial resistance, a major public health challenge. Here we have addressed dendrimers, attractive molecules in pharmaceutical innovation and development displaying broad biological activity. Triazine-based dendrimers were fully synthesized in the solid phase, and their antimicrobial activity and some insights into their mechanisms of action were explored. Triazine is present in a large number of compounds with highly diverse biological targets with broad biological activities and could be an excellent branching unit to accommodate peptides. Our results show that the novel peptide dendrimers synthesized have remarkable antimicrobial activity against Gram-negative bacteria (E. coli and P. aeruginosa) and suggest that they may be useful in neutralizing the effect of efflux machinery on resistance.

Funder

National Research Foundation (NRF) of South Africa

MARATO TV3 Foundation

Publisher

MDPI AG

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