da Silva Gloria Maria, de Souza Daniel Henrique Berto, Waitman Karoline B, Ebram Matteo Celano, Fessel Melissa R, Zainescu Iuliu Cezar, Portaro Fernanda C, Heras Montse, de Andrade Sonia A
Laboratory of Pain and Signaling, Butantan Institute, São Paulo, SP, Brazil.
Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.
J Venom Anim Toxins Incl Trop Dis. 2021 Jan 15;27:e20200066. doi: 10.1590/1678-9199-JVATITD-2020-0066. eCollection 2021.
In Central and South America, snakebite envenomation is mainly caused by spp. snakes, whose venoms feature significant biochemical richness, including serine proteases. The available bothropic antivenoms are efficient in avoiding fatalities, but do not completely neutralize venom serine proteases, which are co-responsible for some disorders observed during envenomation.
In order to search for tools to improve the antivenom's, 6-mer peptides were designed based on a specific substrate for venom serine proteases, and then synthesized, with the intention to selectively inhibit these enzymes.
Using batroxobin as a snake venom serine protease model, two structurally similar inhibitor peptides were identified. When tested on venom, one of the new inhibitors displayed a good potential to inhibit the activity of the venom serine proteases. These inhibitors do not affect human serine proteases as human factor Xa and thrombin, due to their selectivity.
Our study identified two small peptides able to inhibit bothropic serine proteases, but not human ones, can be used as tools to enhance knowledge of the venom composition and function. Moreover, one promising peptide (pepC) was identified that can be explored in the search for improving spp. envenomation treatment.
在中美洲和南美洲，蛇咬伤中毒主要由 属蛇类引起，其毒液具有显著的生化多样性，包括丝氨酸蛋白酶。现有的矛头蝮抗蛇毒血清在避免死亡方面是有效的，但不能完全中和毒液丝氨酸蛋白酶，而这些酶是中毒期间观察到的一些病症的共同成因。
为了寻找改进抗蛇毒血清的工具，基于矛头蝮毒液丝氨酸蛋白酶的一种特定底物设计了6肽，然后进行合成，旨在选择性抑制这些酶。
以巴曲酶作为蛇毒丝氨酸蛋白酶模型，鉴定出两种结构相似的抑制肽。在矛头蝮毒液上进行测试时，其中一种新抑制剂显示出良好的抑制毒液丝氨酸蛋白酶活性的潜力。由于其选择性，这些抑制剂不会影响人丝氨酸蛋白酶，如人凝血因子Xa和凝血酶。
我们的研究鉴定出两种能够抑制矛头蝮丝氨酸蛋白酶而不抑制人丝氨酸蛋白酶的小肽，可作为增进对毒液组成和功能了解的工具。此外，还鉴定出一种有前景的肽（pepC）可用于探索改进矛头蝮中毒的治疗方法。
