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Recombinant and Chimeric Disintegrins in Preclinical Research

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 patho...

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Autores principales: David, Victor, Succar, Barbara Barbosa, de Moraes, João Alfredo, Saldanha-Gama, Roberta Ferreira Gomes, Barja-Fidalgo, Christina, Zingali, Russolina Benedeta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116119/
https://www.ncbi.nlm.nih.gov/pubmed/30087285
http://dx.doi.org/10.3390/toxins10080321
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author David, Victor
Succar, Barbara Barbosa
de Moraes, João Alfredo
Saldanha-Gama, Roberta Ferreira Gomes
Barja-Fidalgo, Christina
Zingali, Russolina Benedeta
author_facet David, Victor
Succar, Barbara Barbosa
de Moraes, João Alfredo
Saldanha-Gama, Roberta Ferreira Gomes
Barja-Fidalgo, Christina
Zingali, Russolina Benedeta
author_sort David, Victor
collection PubMed
description 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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spelling pubmed-61161192018-08-31 Recombinant and Chimeric Disintegrins in Preclinical Research David, Victor Succar, Barbara Barbosa de Moraes, João Alfredo Saldanha-Gama, Roberta Ferreira Gomes Barja-Fidalgo, Christina Zingali, Russolina Benedeta Toxins (Basel) Review 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. MDPI 2018-08-07 /pmc/articles/PMC6116119/ /pubmed/30087285 http://dx.doi.org/10.3390/toxins10080321 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
David, Victor
Succar, Barbara Barbosa
de Moraes, João Alfredo
Saldanha-Gama, Roberta Ferreira Gomes
Barja-Fidalgo, Christina
Zingali, Russolina Benedeta
Recombinant and Chimeric Disintegrins in Preclinical Research
title Recombinant and Chimeric Disintegrins in Preclinical Research
title_full Recombinant and Chimeric Disintegrins in Preclinical Research
title_fullStr Recombinant and Chimeric Disintegrins in Preclinical Research
title_full_unstemmed Recombinant and Chimeric Disintegrins in Preclinical Research
title_short Recombinant and Chimeric Disintegrins in Preclinical Research
title_sort recombinant and chimeric disintegrins in preclinical research
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116119/
https://www.ncbi.nlm.nih.gov/pubmed/30087285
http://dx.doi.org/10.3390/toxins10080321
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