Abstract
The skin secretions of the subfamily Phyllomedusinae have long been known to contain a number of compounds with antimicrobial potential. Herein, a biosynthetic dermaseptin-precursor cDNA was obtained from a Phyllomedusa sauvagii skin secretion-derived cDNA library, and thereafter, the presence of the mature peptide, namely dermaseptin-PS3 (DPS3), was confirmed by LC–MS/MS. Moreover, this naturally occurring peptide was utilized to design two analogues, K5, 17-DPS3 (introducing two lysine residues at positions 5 and 17 to replace acidic amino acids) and L10, 11-DPS3 (replacing two neutral amino acids with the hydrophobic amino acid, leucine), improving its cationicity on the polar/unipolar face and hydrophobicity in a highly conserved sequence motif, respectively. The results in regard to the two analogues show that either increasing cationicity, or hydrophobicity, enhance the antimicrobial activity. Also, the latter analogue had an enhanced anticancer activity, with pretreatment of H157 cells with 1 µM L10, 11-DPS3 decreasing viability by approximately 78%, even though this concentration of peptide exhibited no haemolytic effect. However, it must be noted that in comparison to the initial peptide, both analogues demonstrate higher membrane-rupturing capacity towards mammalian red blood cells.
Highlights
Of the many anuran skin-derived peptides that are known, dermaseptin and dermaseptin-like peptides are the most remarkable candidates for developing new antibiotics in Hylidae frogs [1,2,3]. there is much heterogeneity in either the peptide sequence, or length, among dermaseptins, the family shares several common structural characteristics, including Trp at positionToxins 2018, 10, 320; doi:10.3390/toxins10080320 www.mdpi.com/journal/toxins3 and a conserved sequence of AA(G)KAALG(N)A in the mid-region [4]
Dermaseptins commonly possess a high propensity to adopt an α-helical conformation in hydrophobic media, since the first dermaseptin peptide with 80% of α-helical conformation was isolated from Hylidae frogs [3,5,6]
In general, approximately half of AMP amino acid residues are hydrophobic, and their hydrophobicity and their activity can be altered by changing the number of Leu, Ile and Val residues in these peptides
Summary
Of the many anuran skin-derived peptides that are known, dermaseptin and dermaseptin-like peptides are the most remarkable candidates for developing new antibiotics in Hylidae frogs [1,2,3]. there is much heterogeneity in either the peptide sequence, or length, among dermaseptins, the family shares several common structural characteristics, including Trp at positionToxins 2018, 10, 320; doi:10.3390/toxins10080320 www.mdpi.com/journal/toxins3 and a conserved sequence of AA(G)KAALG(N)A in the mid-region [4]. It is believed that changing the number of positive charges present in an AMP can likely change its membrane binding ability, resulting in a change in antimicrobial activity. In general, approximately half of AMP amino acid residues are hydrophobic, and their hydrophobicity and their activity can be altered by changing the number of Leu, Ile and Val residues in these peptides. Both antibacterial and haemolytic activities of these AMPs tend to get increased simultaneously by increasing the hydrophobicity, due to the fact that the hydrophobic groups play a key role in their insertion into the cell membrane [10]
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