Schistocins: Novel antimicrobial peptides encrypted in the Schistosoma mansoni Kunitz Inhibitor SmKI-1.

BACKGROUND: Here we describe a new class of cryptides (peptides encrypted within a larger protein) with antimicrobial properties, named schistocins, derived from SmKI-1, a key protein in Shistosoma mansoni survival. This is a multi-functional protein with biotechnological potential usage as a therapeutic molecule in inflammatory diseases and to control schistosomiasis. METHODS: We used our algorithm enCrypted, to perform an in silico proteolysis of SmKI-1 and a screening for potential antimicrobial activity. The selected peptides were chemically synthesized, tested in vitro and evaluated by both structural (CD, NMR) and biophysical (ITC) studies to access their structure-function relationship. RESULTS: EnCrypted was capable of predicting AMPs in SmKI-1. Our biophysical analyses described a membrane-induced conformational change from random coil-to-α-helix and a peptide-membrane equilibrium for all schistocins. Our structural data allowed us to suggest a well-known mode of peptide-membrane interaction in which electrostatic attraction between the cationic peptides and anionic membranes results in the bilayer disordering. Moreover, the NMR H/D exchange data with the higher entropic contribution observed for the peptide-membrane interaction showed that schistocins have different orientations upon the membrane. CONCLUSIONS: This work demonstrate the robustness for using the physicochemical features of predicted peptides in the identification of new bioactive cryptides. Besides, it demonstrates the relevance of combining these analyses with biophysical methods to understand the peptide-membrane affinity and improve further algorithms. GENERAL SIGNIFICANCE: Bioprospecting cryptides can be conducted through data mining of protein databases demonstrating the success of our strategy. The peptides-based agents derived from SmKI-1 might have high impact for system-biology and biotechnology.

Antimicrobial alumina nanobiostructures of disulfide- and triazole-linked peptides: Synthesis, characterization, membrane interactions and biological activity.

Due to the its physical-chemical properties, alumina nanoparticles have potential applications in several areas, such as nanobiomaterials for medicinal or orthodontic implants, although the introduction of these devices poses a serious risk of microbial infection. One convenient strategy to circumvent this problem is to associate the nanomaterials to antimicrobial peptides with broad-spectrum of activities. In this study we present two novel synthesis approaches to obtain fibrous type alumina nanoparticles covalently bound to antimicrobial peptides. In the first strategy, thiol functionalized alumina nanoparticles were linked via disulfide bond formation to a cysteine residue of an analog of the peptide BP100 containing a four amino acid spacer (Cys-Ala-Ala-Ala). In the second strategy, alumina nanoparticles were functionalized with azide groups and then bound to alkyne-decorated analogs of the peptides BP100 and DD K through a triazole linkage obtained via a copper(I)-catalyzed cycloaddition reaction. The complete physical-chemical characterization of the intermediates and final materials is presented along with in vitro biological assays and membrane interaction studies, which confirmed the activity of the obtained nanobiostructures against both bacteria and fungi. To our knowledge, this is the first report of aluminum nanoparticles covalently bound to triazole-peptides and to a disulfide bound antimicrobial peptide with high potential for biotechnological applications.