Next Article in Journal
Effects of Heme Modulation on Ovophis and Trimeresurus Venom Activity in Human Plasma
Previous Article in Journal
Biological Activities of Cationicity-Enhanced and Hydrophobicity-Optimized Analogues of an Antimicrobial Peptide, Dermaseptin-PS3, from the Skin Secretion of Phyllomedusa sauvagii
Article Menu

Export Article

Open AccessReview
Toxins 2018, 10(8), 321; https://doi.org/10.3390/toxins10080321

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.
Received: 26 June 2018 / Revised: 23 July 2018 / Accepted: 27 July 2018 / Published: 7 August 2018
(This article belongs to the Special Issue From Toxins to Drugs)
View Full-Text   |   Download PDF [1157 KB, uploaded 7 August 2018]   |  

Abstract

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. View Full-Text
Keywords: Snake venom disintegrin; integrin; cancer Snake venom disintegrin; integrin; cancer
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

David, V.; Barbosa Succar, B.; Alfredo de Moraes, J.; Ferreira Gomes Saldanha-Gama, R.; Barja-Fidalgo, C.; Benedeta Zingali, R. Recombinant and Chimeric Disintegrins in Preclinical Research. Toxins 2018, 10, 321.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top