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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

PEGylation: A Successful Approach to Improve the Biopharmaceutical Potential of Snake Venom Thrombin-Like Serine Protease

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da-Silva-Freitas, Debora [1] ; Boldrini-Franca, Johara [1] ; Arantes, Eliane Candiani [1]
Total Authors: 3
[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, BR-14040903 Ribeirao Preto, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: PROTEIN AND PEPTIDE LETTERS; v. 22, n. 12, p. 1133-1139, 2015.
Web of Science Citations: 3

PEGylation is considered a successful technique to enhance the therapeutic and biotechnological potentials of peptides, proteins, toxins and drugs. The conjugation of polyethylene glycol (PEG) increases the size and molecular weight of conjugated molecule and improves its pharmacokinetics and pharmacodinamics by increasing water solubility, protecting from enzymatic degradation, reducing renal clearance and limiting immunogenic and antigenic reactions. These features are very useful for therapeutic proteins, since PEGylated proteins exhibit high stability and very low immunogenicity, ensuring a sustained clinical response with minimal dose and less frequent administration. The modification of snake venom toxins by PEGylation is a promising strategy to increase the use of these biomolecules in clinical practice, which has been limited by side effects of immune reactions in patients. Thrombin-like serine protease from Crotalus durissus collilineatus (SPCdc) is able to convert fibrinogen into fibrin and presents potential therapeutic application in cases of myocardial infarction, ischemic stroke and other thrombotic and vascular disorders. In this study we modified the SPCdc by site-specific PEGylation, producing the unique conjugate of molecular mass around 35 kDa, named SPCdc-PEG. Unexpectedly, the K-m of the PEGylated enzyme (K-m = 0.447 mM +/- 0.025) was smaller than that of the native enzyme (K-m = 0.770 mM +/- 0.020), indicating that PEG-SPCdc has a higher affinity for the substrate TAME than SPCdc. Additionally, the values of K-cat/K-m (1163 mM.min(-1), for SPCdc-PEG and 350 mM.min(-1), for SPCdc) showed that PEGylated enzyme has higher catalytic efficiency than the native form. These results demonstrated the relevant biopharmaceutical potential of SPCdc-PEG. (AU)

FAPESP's process: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis
Grantee:Suely Vilela
Support type: Research Projects - Thematic Grants
FAPESP's process: 08/11688-5 - Snake venomics and antivenomics of Crotalus durissus subspecies from Brazil and expression of a protease of biotechnological interest cloned from C. d. collilineatus venom gland
Grantee:Johara Boldrini França
Support type: Scholarships in Brazil - Doctorate