Enhancing the Cytotoxicity and Apoptotic Efficacy of Parasporin-2-Derived Variants (Mpp46Aa1) on Cancer Cell Lines.

Parasporin PS2Aa1, recently renamed Mpp46Aa1, is an anti-cancer protein known for its selectivity against various human cancer cell lines. We genetically modified native PS2Aa1 to create a library of approximately 100 mutants. From this library, we selected promising mutants based on their half-maximal inhibitory concentration (IC) and sequence variations.

Toxic Determination of Cry11 Mutated Proteins Obtained Using Rational Design and Its Computational Analysis.

Cry11 proteins are toxic to , the vector of dengue, chikungunya, and Zika viruses. Cry11Aa and Cry11Bb are protoxins, which when activated present their active-toxin form in two fragments between 30 and 35 kDa respectively. Previous studies conducted with Cry11Aa and Cry11Bb genes using DNA shuffling generated variant 8, which presented a deletion in the first 73 amino acids and one at position 572 and 9 substitutions including L553F and L556W.

Site-Directed Mutants of Parasporin PS2Aa1 with Enhanced Cytotoxic Activity in Colorectal Cancer Cell Lines.

Parasporin 2 has cytotoxic effects against numerous colon cancer cell lines, making it a viable alternative to traditional treatments. However, its mechanism of action and receptors remain unknown. In this study, site-directed mutagenesis was used to obtain PS2Aa1 mutants with variation in domain I at positions 256 and 257.

Computational study, synthesis and evaluation of active peptides derived from Parasporin-2 and spike protein from Alphacoronavirus against colorectal cancer cells.

Parasporin-2Aa1 (PS2Aa1) is a toxic protein of 37 KDa (30 kDa, activated form produced by proteolysis) that was shown to be cytotoxic against specific human cancer cells, although its mechanism of action has not been elucidated yet. In order to study the role of some native peptide fragments of proteins on anticancer activity, here we investigated the cytotoxic effect of peptide fragments from domain-1 of PS2Aa1 and one of the loops present in the binding region of the virus spike protein from Alphacoronavirus (HCoV-229E), the latter according to scientific reports, who showed interaction with the human APN (h-APN) receptor, evidence corroborated through computational simulations, and thus being possible active against colon cancer cells. Peptides namely P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa were synthesized using the Fmoc solid-phase synthesis and characterized by mass spectrometry (MS).

Generation of Cry11 Variants of by Heuristic Computational Modeling.

Directed evolution methods mimic in vitro Darwinian evolution, inducing random mutations and selective pressure in genes to obtain proteins with enhanced characteristics. These techniques are developed using trial-and-error testing at an experimental level with a high degree of uncertainty. Therefore, in silico modeling of directed evolution is required to support experimental assays.