Insulin derivatives

Weiland M, Brandenburg C, Brandenburg D et al (1990) Antagonistic effects of a covalently dimerized insulin derivative on insulin receptors in 3T3-L1 adipocytes. Proc Natl Acad Sci USA 87 1154-1158... 

Insulin derivatives lb 401 lodate anions la 188,190 lb 307 Iodine staining lb 278 Iodine-azide reaction lb 85,301-304 Iodide anions la 190 lb 76,77,128,129 Iodide vapor la 46,64,78 lodination la 66... 

The RP-HPLC polishing step not only removes E. coli-derived impurities, but also effectively separates modified insulin derivatives from the native insulin product. The resultant extremely low levels of impurities remaining in these insulin preparations fail to elicit any significant immunological response in diabetic recipients. 

Visser, N.F. et al. 2003. On-line SPE-CE for the determination of insulin derivatives in biological fluids. J. Pharm. Biomed. Anal. 33 451. 

Visser N.F.C., Lingeman H., and Irth H., 2003. Online SPE-RP-LC for the determination of insulin derivatives in biological matrices. J Pharm Biomed Anal 32 295. 

ES-MS of insulin-derived growth factor and minor impurities. 

Structure-Activity Correlations. This detailed knowledge of the three-dimensional structure of insulin led to the recognition that its biological activity resides in an area of the molecule rather than in specific amino acid residues, just as dimerization and further association of the molecule also depend on an intact spatial structure. The foregoing concept is corroborated by structural modifications of the hormone. The last three amino acids of the B chain can be removed without a loss of activity, but cleavage of the C-terminal of the A chain (Asn ) results in a total loss of activity. Amino acids can be replaced inside the chains only if such substitution does not change the overall geometry of the molecule. The structure-activity relationships of insulin derivatives are inconsistent and not always comparable. 

Welinder, B.S. (1971). Isoelectric focusing of insulin and insulin derivatives. Acta Chem. Scand., 25, 3737-3742. 

BANTING, SIR FREDERICK (1891-1941). A nalive ol Onlario, Canada, Banting did his most important work in enducrinulogy. His brilliant research culminated in the preparation of the antidiabetic hormone that he called insulin, derived from the isles of Langerhans in the pancreas. He received the Nobel prize in medicine for this wurk together with John MacLeod of the University of Toronto. In 1930, the Banting Institute was founded in Toronto. lie was killed in an airplane crash. 

In a more elaborate example, Thamm et al. (1980) selectively removed, by Edman degradation, the N-terminal glycine of the A-chain of an insulin derivative in which the B-chain amino terminus and the B-chain lysine were protected. The new N-terminus was reacted with theN-hydroxysuc-cinimide ester of A-(4-azido-2-nitrophenyl)glycine to yield, after deprotection, a derivative of insulin modified only at the NaA-terminus. The amino protecting group chosen for this procedure was the base labile, methylsulfonylethyloxycarbonyl. 

Table X. Biological Activity of Human Insulin Derivatives...

Most of the insulins derived from beef and pork have been largely replaced by the human form synthesized utilizing recombinant DNA technology. 

Most of the insulins derived from beef and pork have been largely replaced by the human form, synthesized utilizing recombinant DNA technology. For example, lispro insulin is synthesized by recombinant DNA technology, using a non-pathogenic strain of E. coli. 

Humulin products (Eli Lilly Company) contain recombinant human insulin derived from Escherichia coli Novolin products (Novo Nordisk) are recombinant human insulin derived from Saccharomyces cerevisiae both companies also sell other forms of recombinant human insulin and may have additional forms (formulations or new drugs) in clinical trials. 

The term immunoreactive insulin is used in reference to assays that may recognize, in addition to insulin, substrates that share antigenic epitopes with insulin. Examples include proinsulin, proinsuHn conversion intermediates, and insulin derivatives, produced by gly-cation or dimerization. 

Jars MU, Hvass A, Waaben D. Insulin aspart (Asp Human insulin) derivatives formed in pharmaceutical solutions. Pharm Res 2002 19(5) 621-628. 

Lenz, V.J. Gattner, H.-G. Leithauser, M. Brandenburg, D. Wolbner, A. Hocker, H. Proteolyses of a fluorogenic insulin derivative and native insulin in reversed micelles monitored by fluorescence emission, reversed-phase high-performance liquid chromatography, and capillary zone electrophoresis. Anal.Biochem., 1994, 221, 85-93... 

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