Format

Send to

Choose Destination
Cytokine Growth Factor Rev. 2015 Dec;26(6):637-45. doi: 10.1016/j.cytogfr.2015.07.012. Epub 2015 Jul 6.

Human consensus interferons: Bridging the natural and artificial cytokines with intrinsic disorder.

Author information

1
Protective and Therapeutic Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute GEBRI, City for Scientific Research and Technology Applications, New Borg EL Arab, 21934 Alexandria, Egypt.
2
Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, P.O. Box 80203, Jeddah 21589, Saudi Arabia; Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA; Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, 142290 Moscow Region, Russia. Electronic address: vuversky@health.usf.edu.
3
Protective and Therapeutic Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute GEBRI, City for Scientific Research and Technology Applications, New Borg EL Arab, 21934 Alexandria, Egypt; Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, P.O. Box 80203, Jeddah 21589, Saudi Arabia. Electronic address: redwan1961@yahoo.com.

Abstract

The consensus interferons are artificially engineered proteins that combine most of the therapeutic features of natural human α-interferons and show high anti-cancer and anti-viral activities. Egyptian patients infected with hepatitis C virus (HCV) genotype 4 show lower responses to interferon (IFN) therapy than the distributed worldwide patients infected with the other HCV genotypes. Numerous studies have reported that patients with hepatitis C who have not responded to a previous standard IFN-alpha therapy or those who relapsed following treatment cessation may benefit from retreatment with consensus IFN-α (cIFN-α). IFNs-α are shown here to have functionally important disordered regions. Furthermore, a strong correlation is established between the peculiarities of disorder profiles of these proteins and their known structural features. Intrinsic disorder profiles of existing cIFNs-α possess remarkable similarity to the consensus disorder profile calculated as averaged disorder predispositions of all human IFNs-α. If the peculiarities of disorder distribution within the protein sequence are related to protein functionality, then comparison of the disorder profiles of artificial cIFNs (query profiles) with the averaged disorder predisposition profile of human IFNs-α (target profile) can be used in the design of novel cIFNs. The goal here would be to achieve a close similarity between the query and target profiles by manipulating the cIFN sequence.

KEYWORDS:

Artificial protein; Consensus interferon; Hepatitis C virus; Interferon; Protein intrinsic disorder

PMID:
26169931
DOI:
10.1016/j.cytogfr.2015.07.012
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center