Repository of Research and Investigative Information

Repository of Research and Investigative Information

Dezful University of Medical Sciences

A Precisely Designed Immunotoxin Against VCAM1 Consisting of a Humanized Antibody Variable Domain Fused to Granzyme: An In Silico Approach

(2019) A Precisely Designed Immunotoxin Against VCAM1 Consisting of a Humanized Antibody Variable Domain Fused to Granzyme: An In Silico Approach. International Journal of Peptide Research and Therapeutics. ISSN 15733149 (ISSN)

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Official URL: https://www2.scopus.com/inward/record.uri?eid=2-s2...

Abstract

Atherosclerosis is a complex disease related to cardiovascular disorders and is one of the most considerable causes of mortality worldwide. It has been shown that the immune system plays a pivotal role in generating atherosclerosis plaques. The atherosclerosis plaques form via activation of endothelial cells by recruiting adhesion molecules such as VCAM1. Therefore, VCAM1 could be considered as a suitable target to design immune-therapeutics. In this regard, we have lunched an in silico approach to design an immunotoxin against VCAM1. The structure of an anti-VCAM1 antibody was predicted using homology modeling software. The structure of the predicted chains were linked by (Gly 4 Ser) 3 linker. Then, using various modeling software the structure of the GrB was linked to the antibody structure via an adaptor sequence. The final structure was energy minimized, evaluated for accuracy and characterized for its biological properties. Our results indicated that the employed structure prediction method has successfully managed to model the immunotoxin structure. Moreover, our results indicated that the designed immunotoxin is capable of VCAM1 interaction with proper orientation involving its C–D loop. In conclusion it should be pointed out that, the employed in silico approach could pave the way for precise and accurate design of immune-therapeutic agents against cancer. Using this approach we have designed an immunotoxin capable of VCAM1 targeting in a proper orientation and following cancer cell destruction by the toxin domain of the molecule. © 2019, Springer Nature B.V.

Item Type: Article
Keywords: Atherosclerosis Bioinformatics Immunotoxin VCAM1
Journal or Publication Title: International Journal of Peptide Research and Therapeutics
Journal Index: Scopus
Identification Number: https://doi.org/10.1007/s10989-019-09822-6
ISSN: 15733149 (ISSN)
Depositing User: مهندس مهدی شریفی
URI: http://eprints.dums.ac.ir/id/eprint/430

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