Part:BBa_K4075004
Antimicrobial Peptide DRS-N1
Dermaseptin-N1 (DRS-N1) peptide is the shortest dermaseptin ever described, and this short cationic peptide contains 20 amino acids and was isolated from the skin secretion of Phyllomedusa nordestina. DRS-N1 was in vitro evaluated positively against the promastigote form of L. infantum. Also, the peptide resulted in very low toxicity for mammalian cells [1].
Sequence and Features
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000COMPATIBLE WITH RFC[1000]
Profile
Name: Dermaseptin-N1(DRS-N1)
Base Pairs: 66 bp
Origin: Phyllomedusa nordestina
Properties: Antimicrobial peptide with leishmanicidal potential
Design considerations: Codon optimization for E. coli
Source: UniProt(P0DTD4)and [1]
Usage and Biology
Dermaseptins (DRSs) are peptides produced by Hylid frogs, a group of alfa-helical shaped polycationic and short peptides (21-34 residues) containing a highly preserved tryptophan residue on N-terminal 3rd position, with hydrophobic residues and the polar cationic residues clusters in opposite sides [2]. It shows strong conservation of precursor pro-domains, containing a signal peptide and acidic pro-peptide that inactivate the peptide until the target action region [3]. Regarding safety concerns, these peptides show effectiveness in vitro against many pathogens (i.e. bacterias, parasites, viruses, etc) and several human cancer types. Their negatively charged membranes increase the interaction with DRSs cationic peptides, which induce membrane destabilization and cell lysis. Although negatively charged membranes are present in normal erythrocytes, there is not great interaction with DRSs. However, in vivo and clinical DRSs experiments remains to be investigated to understand the safety aspects [2].
The UNILA_LatAm 2021 team selected pro-peptides to act as an inactivator for leishmanicidal candidates such as CAM-W (BBa_K4075005), DRS-N1 (BBa_K4075004), DRS-S1 (BBa_K4075006) e DRS-H3 (BBa_K4075007). The composite structure contains a trypsin cleavage site between pro-peptide and AMP-activated form, this site allows the proAMPs to be split after trypsin digestion and the AMP-activated form restores the antimicrobial capacity.
| Pro-peptide | AMP | Final Composite |
|---|---|---|
| DRS-H3 pro-peptide | DRS-N1 | BBa_K4075008 |
| E10 pro-peptide | CAM-W | BBa_K4075009 |
| DRS-S1 pro-peptide | DRS-S1 | BBa_K4075010 |
| DRS-H3 pro-peptide | DRS-H3 | BBa_K4075011 |
| E10 pro-peptide | DRS-N1 | BBa_K4075012 |
[1] Brand, G. D. et al. (2013) "The Skin Secretion of the Amphibian Phyllomedusa nordestina: A source of Antimicrobial and Antiprotozoal Peptides." MDPI Molecules 18(6): 7058-7070.
[2] Bartels E. J. et al. (2019) "Dermaseptins, Multifunctional Antimicrobial Peptides: A review of Their Pharmacology, Effectivity, Mechanism of Action, and Possible Future Directions." Frontiers in Pharmacology (10):1321
[3] Nicolas, P. et al.(2009) "The dermaseptin superfamily: A gene-based combinatorial library of antimicrobial peptides." Biochimica et Biophysica Acta (BBA) - Biomembranes. 1778(8):1537-1550.
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