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Sci Rep. 2016 Mar 17;6:23320. doi: 10.1038/srep23320.

Looking at the carcinogenicity of human insulin analogues via the intrinsic disorder prism.

Author information

1
Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia.
2
Therapeutic and Protective Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City for Scientific Research and Technology Applications, New Borg EL-Arab 21934, Alexandria, Egypt.
3
Department of Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia.
4
Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
5
Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russian Federation, Russia.

Abstract

Therapeutic insulin, in its native and biosynthetic forms as well as several currently available insulin analogues, continues to be the protein of most interest to researchers. From the time of its discovery to the development of modern insulin analogues, this important therapeutic protein has passed through several stages and product generations. Beside the well-known link between diabetes and cancer risk, the currently used therapeutic insulin analogues raised serious concerns due to their potential roles in cancer initiation and/or progression. It is possible that structural variations in some of the insulin analogues are responsible for the appearance of new oncogenic species with high binding affinity to the insulin-like growth factor 1 (IGF1) receptor. The question we are trying to answer in this work is: are there any specific features of the distribution of intrinsic disorder propensity within the amino acid sequences of insulin analogues that may provide an explanation for the carcinogenicity of the altered insulin protein?

PMID:
26983499
PMCID:
PMC4794765
DOI:
10.1038/srep23320
[Indexed for MEDLINE]
Free PMC Article

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