Snake Venom Peptides: Tools of Biodiscovery

Abstract

Nature endowed snakes with a lethal secretion known as venom, which has been fine-tuned over millions of years of evolution. Snakes utilize venom to subdue their prey and to survive in their natural habitat. Venom is known to be a very poisonous mixture, consisting of a variety of molecules, such as carbohydrates, nucleosides, amino acids, lipids, proteins and peptides. Proteins and peptides are the major constituents of the dry weight of snake venoms and are of main interest for scientific investigations as well as for various pharmacological applications. Snake venoms contain enzymatic and non-enzymatic proteins and peptides, which are grouped into different families based on their structure and function. Members of a single family display significant similarities in their primary, secondary and tertiary structures, but in many cases have distinct pharmacological functions and different bioactivities. The functional specificity of peptides belonging to the same family can be attributed to subtle variations in their amino acid sequences. Currently, complementary tools and techniques are utilized to isolate and characterize the peptides, and study their potential applications as molecular probes, and possible templates for drug discovery and design investigations.

Development and Challenges of Antimicrobial Peptides for Therapeutic Applications

“…These features optimize their pharmacokinetics and extend their elimination half-life so that they resist enzymatic degradation. The APD contains 3156 AMPs, 98% of which were discovered in nature [13]: many, in fact, were extracted from the skin secretions of frogs [44,[113][114][115] or are toxins from other species, e.g., bees, snakes, and wasps [86,116,117]. In contrast, all the FDA-approved AMPs were discovered in or derived from Gram-positive bacteria commonly found in the soil: Brevibacillus brevis (gramicidin), Streptomyces roseosporus (daptomycin), Amycolatopsis orientalis (vancomycin, which is the prototype of oritavancin, dalbavancin, and telavancin), and Paenibacillus polymyxa (colistin) [118].…”

Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis

“…These venoms comprise 50-200 components distributed in dominant and secondary families which can be presented in multiple proteins and peptides isoforms (Vonk et al, 2011;Slagboom et al, 2017;Tasoulis and Isbister, 2017). The dominant families are secreted phospholipases A 2 (PLA2s), snake venom metalloproteinases (SVMP), snake venom serine proteases (SVSP), and three-finger peptides (3FTX), while the secondary families comprise cysteine-rich secretory proteins, Lamino acid oxidases, kunitz peptides, C-type lectins, disintegrins, and natriuretic peptides (Slagboom et al, 2017;Tasoulis and Isbister, 2017;Munawar et al, 2018). Interestingly, snake venom composition varies interspecifically (Fry et al, 2008;Tasoulis and Isbister, 2017), as well as intraspecifically, with many factors influencing this diversity including age (Dias et al, 2013), gender (Menezes et al, 2006;Zelanis et al, 2016), location (Durban et al, 2011;Goncalves-Machado et al, 2016), diet (Barlow et al, 2009), and season (Gubensek et al, 1974).…”

Extended snake venomics by top-down in-source decay: Investigating the newly discovered Anatolian Meadow viper subspecies,Vipera anatolica senliki

“…The non-reduced intact mass signal of fraction 11 shows a mass of 6,630.1 Da, which is an indicator for a Kunitz-type serine protease inhibitor ( Figure 3A ). 68, 69 The comparison with the reduced intact mass (6,636.2 Da) reveals a mass shift of Δ6.1 Da (corresponding to three disulfide bridges), which confirms the Kunitz-type architecture. Furthermore we were able to identify several PLA 2 proteoforms in fractions 14 and 15 by disulfide bond mapping ( Figure 3B ).…”