Part:BBa_K2486108
Dermaseptin K4K20-S4 (no stop codon)
[theoretical part] [not assembled, not synthesized, not sent, not characterized]
Derivatives of the peptide Dermaseptin S4, such as Dermaseptin K4K20-S4, were shown to block growth of the malaria parasite (PMID:10952593).
Usage and Biology - UNILA_LatAm Contribution
Dermaseptins (DRSs) are peptides produced by Hylid frogs, a group of ɑ-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 [1]. 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 [2]. Regarding safety concerns, these peptides show effectiveness in vitro against many pathogens (i.e. bacterias, parasites, viruses, etc) and several human cancer types. The negatively charged membranes of some pathogens 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 [1].
Many antimicrobial peptides (AMPs) are synthesized, delivered or stored in an inactive form, known as AMPs precursors (proAMPs), that require proteolytic cleavage to become active (i.e. cathelicidins, defensins, etc). Therefore, gene expression is not the primary regulatory mechanism, and the abundance of appropriate proteases to activate it became a potential strategy to regulate it. These precursor forms often have a tripartite structure as peptide signal, acidic pro-peptide (or pro-domain) and the antimicrobial itself [3,4]. The acidic pro-peptide has charge densities that neutralize the positive charge of AMPs. The electrostatic neutralization turns the AMPs less toxic in an inactive form, which molecularly is still unclear [3].
This mechanism has been exploited for biotechnological applications as efficiently peptide recombinant production, reducing the toxicity to the host bacteria, or the pro-drug strategy, whereas can activate the AMP upon the presence of a specific pathogen [3]. The iGEM UNILA LatAm 2021 team identified in the literature two potential dermaseptin propeptides that can be used to modulate the cytotoxic response. This year the team sought to evaluate natural dermaspetin propeptides in modulating the response of dermaseptins, such as DRS-N1 (BBa_K4075008)
[1]Bartels J. et al. Dermaseptins, Multifunctional Antimicrobial Peptides: A Review of Their Pharmacology, Effectivity, Mechanism of Action, and Possible Future Directions.
[2] Nicolas, P., & el Amri, C. (2009). The dermaseptin superfamily: A gene-based combinatorial library of antimicrobial peptides. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1788(8), 1537–1550.
[3]Júnior, N. G. O. et al. (2018). An acidic model pro-peptide affects the secondary structure, membrane interactions and antimicrobial activity of a crotalicidin fragment. Scientific Reports 2018 8:1, 8(1), 1–11.
[4] Mahlapuu, M. et al. (2016). Antimicrobial Peptides: An Emerging Category of Therapeutic Agents. Frontiers in Cellular and Infection Microbiology, 0(DEC), 194.
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]
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