Repository of Research and Investigative Information

Repository of Research and Investigative Information

Baqiyatallah University of Medical Sciences

Structure Based Screening for Inhibitory Therapeutics of CTLA-4 Unveiled New Insights About Biology of ACTH

(2020) Structure Based Screening for Inhibitory Therapeutics of CTLA-4 Unveiled New Insights About Biology of ACTH. International Journal of Peptide Research and Therapeutics. pp. 849-859. ISSN 1573-3149

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Abstract

Although the biology of adrenocorticotropic hormone (ACTH) protein has already been scrutinized, some functional aspects of its biology are yet to be elucidated in the context of immunological disorders. In this regard, virtual screening of a compound library was performed against the structure of Cytotoxic T-Lymphocyte Associated Protein-4 (CTLA-4) (assessed both spatially and energetically) to discover novel biological functions for ACTH. The results of virtual screening and the MD simulation demonstrated that DB01284 has high binding energy along with proper interaction orientation against CTLA-4 (FG loop) by a clamp like structure. The employed methodology was checked using confirmatory control analyses. Intriguingly, DB01284 belongs to Tetracosactide (already prescribed protein drug for clinical conditions) which is the N-terminal region of ACTH. This is the first study to reveal that ACTH protein binds to the same amino acids of CTLA-4 (FG-loop) as B7 and anti-CTLA-4 antibody binds. In light of this finding, the molecular mechanism of ACTH function in patients suffering from Cushing's Syndrom and the immunological bases for ACTH therapy of multiple sclerosis (MS) patients could be further delineated. Moreover, this finding suggests that ACTH could also act to block CTLA-4 in the context of anticancer immune check point blockade.

Item Type: Article
Keywords: ACTH CTLA-4 Virtual screening Autoimmune diseases experimental autoimmune encephalomyelitis in-vitro acinetobacter-baumannii melanocortin receptors monoclonal-antibodies cell proliferation cushings-syndrome prostate-cancer key role blockade Biochemistry & Molecular Biology
Page Range: pp. 849-859
Journal or Publication Title: International Journal of Peptide Research and Therapeutics
Journal Index: ISI
Volume: 26
Number: 2
Identification Number: https://doi.org/10.1007/s10989-019-09891-7
ISSN: 1573-3149
Depositing User: مهندس مهدی شریفی
URI: http://eprints.bmsu.ac.ir/id/eprint/8805

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