An Overview of Brevinin Superfamily: Structure, Function and Clinical Perspectives

Abstract

SummaryAntimicrobial peptides are the backbone of first-line defense against various microorganisms in the animal kingdom. Thus, not surprisingly, they are gaining attention in the science and medical fields as a rich repository of new pro-drugs. Below, we focus our attention on the Brevinin family of anuran peptides. While most of them show strong antibacterial activities, some, e.g. Brevinin-2R, appear to be promising anticancer molecules, exhibiting better a therapeutic window than widely-use anticancer drugs like doxorubicin. We briefly introduce the field, followed by highlighting the promising therapeutic properties of Brevinins. Next, we provide information about the cloning and phylogenetic aspects of Brevinin genes. In the final paragraphs of this chapter, we discuss possible large-scale production methods of Brevinins, giving examples of some systems that are already in use. Towards the end, we discuss various means of modification of biologic properties of Brevinins, either by chemical modifications or by amino acid substitution and sequence rearrangements. In this context, also other unique properties of Brevinins are briefly mentioned. Finally, we discuss the future of the Brevinin field,particularly highlighting yet to be answered biologic questions, like for example presumed anti-viral and antitumor activities of Brevinin family members.2

Latarcins: versatile spider venom peptides

“…Several LP, e.g., brevinin from frog skin, were shown to kill different tumor cells (Jurkat, BJAB, MCF-7, L929, and A549) at lower concentrations compared to commercial doxorubicin and cisplatin drugs [164]. Peptides are considered to be a novel class of anticancer agents due to their capability to specifically target cancer cells with lower toxicity to normal tissues [66].…”

Biological Properties, Current Applications and Potential Therapeautic Applications of Brevinin Peptide Superfamily

“…Barrel stave model: In this model, antimicrobial activity of peptide is based on the pore formation in the membrane. The polar residues constitute the inner part of the channel, while the hydrophobic ones are in contact with the membrane phospholipids in the outer part (Savelyeva et al 2014). 2.…”

Modification and Targeted Design of N-Terminal Truncates Derived from Brevinin with Improved Therapeutic Efficacy

“…Amphibian skin secretions are a remarkable source of potentially novel therapeutic agents [ 5 ], and amphibian AMPs have demonstrated outstanding efficacy and kill microorganisms via a number of different mechanisms, offering the prospect of avoiding antibiotic-resistance [ 6 ]. The Brevinin-1 peptide family is one of the most ubiquitous AMP families [ 7 ], and since the first Brevinin-1 peptide with broad-spectrum antimicrobial activity was isolated from Rana brevipoda porsa , 985 Brevinin-1 peptides have been deposited into the database [ 8 ]. They share a highly conserved C-terminal disulphide bridged cyclic heptapeptide loop, namely the “Rana Box” [ 9 ].…”