First generation of multifunctional peptides derived from latarcin-3a from Lachesana tarabaevi spider toxin

Abstract

The need for discovering new compounds that can act selectively on pathogens is becoming increasingly evident, given the number of deaths worldwide due to bacterial infections or tumor cells. New multifunctional biotechnological tools are being sought, including compounds present in spider venoms, which have high biotechnological potential. The present work aims to perform the rational design and functional evaluation of synthetic peptides derived from Lachesana tarabaevi spider toxin, known as latarcin-3a. The antimicrobial activity was tested against Gram-positive and -negative bacteria, with minimum inhibitory concentrations (MIC) between 4 and 128 μg.ml−1. Anti-biofilm tests were then performed to obtain MICs, where the peptides demonstrated activity from 4 to 128 μg.ml−1. In vitro cell cytotoxicity assays were carried out from tumor cell lines, lineages C1498, Kasumi-1, K-562, Jurkat, MOLT4, and Raji. Erythrocyte integrity was evaluated in the presence of synthetic peptides analog, which did not promote hemolysis at 128 μg.ml−1. The peptide that showed the best antibacterial activity was Lt-MAP3 and the best antitumor was Lt-MAP2. In conclusion, rational design of multifunctional antimicrobial peptides may be promising alternative tools in the treatment of emerging diseases such as bacterial infections and tumor cells.

Pathophysiology to Risk Factor and Therapeutics to Treatment Strategies on Epilepsy

“…Peptides are molecules that may have a high potential for the treatment and prevention of epileptogenesis, as they are easily absorbed by the blood-brain barrier due to their small size, and they interact with specific targets, promoting a neuroprotective effect [83]. Arginine and lysine-rich cationic peptides exhibit a range of biological activities, including immunomodulation, the blockade of ion channels, and tropism of membranes with lytic or cell penetration action, contributing to potential permeability and access to the central nervous system [84][85][86][87]. Some peptides, such as TAT-NR2B9c, CN-105, and RD2, have a neuroprotective function and can be used for the treatment of ischemic stroke, hemorrhagic stroke, and Alzheimer's disease.…”

Membrane-Active Peptides and Their Potential Biomedical Application

“…A viable solution could be the projection of a mutually reinforcing partnership between them and traditional and/or innovative pharmaceutical formulations [ 155 ] to overcome regular microbial resistance [ 20 ]. As a result, numerous peptide technologies, such as CPPs, peptide–drug conjugates, multifunctional peptides, and technologies emphasizing various administration methods, have been developing as promising alternatives to current therapies for emerging diseases like bacterial infections and tumor cells [ 156 ]. Since therapeutic candidates with dual-target pharmacology exhibit more complex in vivo outcomes than those with single-target pharmacology, producing multifunctional peptides may be challenging.…”