Super-Cationic Peptide Dendrimers-Synthesis and Evaluation as Antimicrobial Agents

Estelle J Ramchuran; Isabel Pérez-Guillén; Linda A Bester; René Khan; Fernando Albericio; Miguel Viñas; Beatriz G de la Torre

doi:10.3390/antibiotics10060695

Super-Cationic Peptide Dendrimers-Synthesis and Evaluation as Antimicrobial Agents

Antibiotics (Basel). 2021 Jun 10;10(6):695. doi: 10.3390/antibiotics10060695.

Authors

Estelle J Ramchuran^{1

2}, Isabel Pérez-Guillén³, Linda A Bester¹, René Khan⁴, Fernando Albericio^{2

5

6}, Miguel Viñas³, Beatriz G de la Torre⁷

Affiliations

¹ Biomedical Resource Unit, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa.
² Peptide Sciences Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, University Road, Westville, Durban 4001, South Africa.
³ Lab Molecular Microbiology & Antimicrobials, Department of Pathology and Experimental Therapeutics, Medical School-IDIBELL, University of Barcelona, Hospitalet, 08907 Barcelona, Spain.
⁴ Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban 4001, South Africa.
⁵ Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), 08034 Barcelona, Spain.
⁶ CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain.
⁷ KRISP, College of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4001, South Africa.

Abstract

Microbial infections are a major public health concern. Antimicrobial peptides (AMPs) have been demonstrated to be a plausible alternative to the current arsenal of drugs that has become inefficient due to multidrug resistance. Herein we describe a new AMP family, namely the super-cationic peptide dendrimers (SCPDs). Although all members of the series exert some antibacterial activity, we propose that special attention should be given to (KLK)₂KLLKLL-NH₂ (G1KLK-L2KL2), which shows selectivity for Gram-negative bacteria and virtually no cytotoxicity in HepG2 and HEK293. These results reinforce the validity of the SCPD family as a valuable class of AMP and support G1KLK-L2KL2 as a strong lead candidate for the future development of an antibacterial agent against Gram-negative bacteria.

Keywords: Gram-negative; Gram-positive; antimicrobial peptides; solid-phase peptide synthesis; therapeutic index.

Grants and funding

#20183530/Fundació la Marató de TV3