Recombinant and Chimeric Disintegrins in Preclinical Research
1
Laboratório de Hemostase e Venenos, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21.941-902, Brazil
2
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21.941-902, Brazil
3
Laboratório de Farmacologia Celular e Molecular, Departamento de Biologia Celular, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20.551-030, Brazil
*
Author to whom correspondence should be addressed.
Toxins 2018, 10(8), 321; https://doi.org/10.3390/toxins10080321
Received: 26 June 2018
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Revised: 23 July 2018
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Accepted: 27 July 2018
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Published: 7 August 2018
(This article belongs to the Special Issue From Toxins to Drugs)
Disintegrins are a family of small cysteine-rich peptides, found in a wide variety of snake venoms of different phylogenetic origin. These peptides selectively bind to integrins, which are heterodimeric adhesion receptors that play a fundamental role in the regulation of many physiological and pathological processes, such as hemostasis and tumor metastasis. Most disintegrins interact with integrins through the RGD (Arg-Gly-Asp) sequence loop, resulting in an active site that modulates the integrin activity. Some variations in the tripeptide sequence and the variability in its neighborhood result in a different specificity or affinity toward integrin receptors from platelets, tumor cells or neutrophils. Recombinant forms of these proteins are obtained mainly through Escherichia coli, which is the most common host used for heterologous expression. Advances in the study of the structure-activity relationship and importance of some regions of the molecule, especially the hairpin loop and the C-terminus, rely on approaches such as site-directed mutagenesis and the design and expression of chimeric peptides. This review provides highlights of the biological relevance and contribution of recombinant disintegrins to the understanding of their binding specificity, biological activities and therapeutic potential. The biological and pharmacological relevance on the newest discoveries about this family of integrin-binding proteins are discussed.
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Keywords:
Snake venom disintegrin; integrin; cancer
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MDPI and ACS Style
David, V.; Succar, B.B.; De Moraes, J.A.; Saldanha-Gama, R.F.G.; Barja-Fidalgo, C.; Zingali, R.B. Recombinant and Chimeric Disintegrins in Preclinical Research. Toxins 2018, 10, 321. https://doi.org/10.3390/toxins10080321
AMA Style
David V, Succar BB, De Moraes JA, Saldanha-Gama RFG, Barja-Fidalgo C, Zingali RB. Recombinant and Chimeric Disintegrins in Preclinical Research. Toxins. 2018; 10(8):321. https://doi.org/10.3390/toxins10080321
Chicago/Turabian StyleDavid, Victor, Barbara Barbosa Succar, João Alfredo De Moraes, Roberta Ferreira Gomes Saldanha-Gama, Christina Barja-Fidalgo, and Russolina Benedeta Zingali. 2018. "Recombinant and Chimeric Disintegrins in Preclinical Research" Toxins 10, no. 8: 321. https://doi.org/10.3390/toxins10080321
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