Loading...
DESIGN OF NOVEL INSULINS WITH CHANGED SELF-ASSOCIATION AND LIGAND BINDING PROPERTIES
Brange, J. Drejer, K. Hansen, J. R. Havelund, S. Kaarsholm, N. C. Melberg, S. G. Soerensen, A, R.
Brange, J.
Drejer, K.
Hansen, J. R.
Havelund, S.
Kaarsholm, N. C.
Melberg, S. G.
Soerensen, A, R.
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
1989
Submitted date
2023-11-03
Files
Loading...
PDF
Adobe PDF, 3.14 MB
Other Titles
Abstract
Different wild type insulins have been used for treatment of diabetes mellitus since Banting and Best (1) isolated insulin for the first time in 1921. This injection therapy has saved many lives but has not been able to reproduce the serum insulin profile obtained by physiological endogenous insulin secretion. The requirements of biosynthesis, processing and storage in the pancreas have put severe constraints on the insulin molecule giving it properties which are not necessary for the biological action of the hormone and which limit the possibilities of obtaining adequate metabolic control in diabetics.The self-association to a hexamer, for example, facilitates proinsulin conversion and its subsequent precipitation as crystals in the storage vesicle (2) but is evidently not related to the interaction of insulin as a monomer to its receptor, and this property delays the transport of insulin from the subcutaneous depot to the circulation (3). Thus pancreatie insulin did not evolve for exogenous administration, and with the aim of producing insulin with improved therapeutical characteristics a whole series of human insulin analogues with changed self-association and ligand binding properties has been developed through molecular modelling and recombinant DNA-technology. Most analogues were designed to have less tendency to associate (4) but a few were also created to possess stronger association or metal-binding properties.
Citation
Advances in protein design, 139 - 144
Journal
DOI
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Book chapter
conference paper
conference paper
Language
en
Description
Series/Report no.
GBF monographs ; Volume 12
ISSN
0930-4320
EISSN
ISBN
3527280243
0895739534
0895739534
ISMN
Gov't Doc #
Sponsors
License
Attribution-NonCommercial-ShareAlike 4.0 International