CyLoP-1: Membrane-active peptide with cell-penetrating and antimicrobial properties

Abstract

CyLoP-1 is a cysteine-rich cell-penetrating peptide derived from nuclear localization sequence of snake toxin, crotamine. The peptide has shown cytoplasmic uptake in mammalian cells at lower concentrations. In the present study, the cell-penetrating and antimicrobial activity of the peptide has been studied by employing mammalian cells, plant cells as well as bacterial and fungal pathogens. The study shows that the peptide acts as an effective CPP and a cargo-delivery vector for not only mammalian cells but also for plant cells. Besides this, the peptide also possesses antimicrobial activity against representative pathogens tested. It is shown to be effective in killing methicillin-resistant Staphylococcus aureus. We have observed that the presence of cysteine residues in the peptide play a major role in conferring cell-penetrating as well as antimicrobial activity to the peptide since there is a significant decline in these activities when cysteine residues are replaced with serine residues. Our findings are significant for the proposition that CyLoP-1 is an efficient membrane-active peptide with both cell-penetrating and antimicrobial activity. Hence, it can be further evaluated for its application in the field of drug-delivery, plant biotechnology and as a peptide-antibiotic.

The effect of turn residues on the folding and cell‐penetrating activity of β‐hairpin peptides and applications toward protein delivery

“…The mechanism in which CPPs enter cells can be affected by both the peptide sequence and the type of attached cargo, with common modes of transport involving direct translocation through the outer membrane or various forms of endocytosis . Although they have different intended functions, lytic anticancer and antimicrobial peptides often share many features with CPPs, such as amphiphilicity, high positive charge content, and the ability to adopt secondary structure when engaging with negatively charged surfaces . For example, our lab previously developed the anticancer peptide SVS1, which acts through a lytic mechanism dependent on the peptide's ability to bind to negatively charged components of cell surfaces and fold into β‐hairpin‐rich structures that disrupt the membrane .…”

Hitchhiking with Nature: Snake Venom Peptides to Fight Cancer and Superbugs

“…Derivatives of crotamine [CyLoP-1 (cytosol localizing peptide 1) and the NrTPs (nucleolar-targeting peptides)] have been designed, with cytosolic and nucleolar localization, respectively, instead of the nuclear distribution pattern of crotamine [149][150][151]. [115] and represented with Jalview v2.11.0 software [116].…”

Design and Validation of a Frugal, Automated, Solid-Phase Peptide Synthesizer

“…A common use of solid-phase peptide synthesis is prototyping therapeutic agents, often small amphiphilic molecules that may function as tags to deliver biopharmaceutical cargo to the cell cytoplasm. Thus, a cell-penetrating peptide based on Cylop-1 was selected for testing on this frugal system [21,22]. Following synthesis, this peptide was characterized by electrospray ionization mass spectrometry (Fig 4).…”