Synthesis and properties of carbonylbis(methionyl)insulin, a proinsulin analogue which is convertible to insulin by cyanogen bromide cleavage

W D Busse, F H Carpenter


The preparation and use of carbonylbis (L-methionine p-nitrophenyl ester) as a reversible cross-linking reagent for insulin are described. The reaction of 1 equiv of reagent with zinc insulin in dimethylformamide in the presence of triethylamine yields as one of the products NalphaA1, NepsilonB29-carbonylbis(methionyl)insulin, (CBM-insulin). The CBM-insulin was characterized by end group analysis and by the products formed on tryptic and chymotryptic cleavage. It possessed 91% of the immunological and 6.5% of the hormonal activity of insulin. Treatment of CBM-insulin with cyanogen bromide (CNBr) in 70% formic acid for 1 h resulted in nearly complete removal of the methionine bridge to yield insulin. A small amount of a side product was removed on DEAE-cellulose at pH 7.2 to give an overall recovery of insulin of 70-80%. Oxidative sulfitolyses of CBM-insulin gave the hexa(S-sulfonate) which was reduced with dithiothreitol to yield reduced CBM-insulin. The latter compound, containing 6 sulfhydryls, exhibited a pH-dependent circular dichroic spectrum. The form at pH 10 exhibited a spectrum typical of random coil which was converted to a form at pH 7.8 which was characterized by a negative extremum at 213 nm. The change in the spec...Continue Reading


Mar 1, 1973·Analytical Biochemistry·D Racusen
Aug 1, 1974·Analytical Biochemistry·T PooleW W Fish
Sep 4, 1974·Journal of the American Chemical Society·W D BusseF H Carpenter
Jun 15, 1973·Biochimica Et Biophysica Acta·D Levy
Nov 1, 1973·Biochemical and Biophysical Research Communications·R Geiger, R Obermeier
Feb 1, 1973·Hoppe-Seyler's Zeitschrift für physiologische Chemie·W D Busse, H G Gattner
Jun 1, 1973·Hoppe-Seyler's Zeitschrift für physiologische Chemie·D Brandenburg, A Wollmer
Jun 25, 1971·Nature·T L BlundellM Vijayan
Jun 1, 1972·Hoppe-Seyler's Zeitschrift für physiologische Chemie·D Brandenburg
Jun 1, 1968·Proceedings of the National Academy of Sciences of the United States of America·D F Steiner, J L Clark
Feb 20, 1970·Biochemical and Biophysical Research Communications·R W Boesel, F H Carpenter
Mar 1, 1972·FEBS Letters·D G. Lindsay
May 1, 1959·Archives of Biochemistry and Biophysics·G L ELLMAN
Mar 1, 1965·The Biochemical Journal·R F DOOLITTLE
Sep 1, 1960·The Journal of Clinical Investigation·A E RENOLDM C SHEPS
Feb 1, 1967·Proceedings of the National Academy of Sciences of the United States of America·D F Steiner, P E Oyer


Jan 1, 1980·Diabetologia·D I DronD Brandenburg
Jan 25, 2013·Journal of the American Chemical Society·Michal Avital-ShmiloviciStephen B H Kent
Oct 20, 2009·Journal of the American Chemical Society·Youhei Sohma, Stephen B H Kent
Feb 5, 2014·Genome Biology and Evolution·José Ignacio ArroyoJuan C Opazo
Aug 18, 2010·Angewandte Chemie·Hans-Jürgen Musiol, Luis Moroder
Apr 1, 1984·Analytical Biochemistry·T W ThannhauserH A Scheraga
May 27, 2017·Angewandte Chemie·Luis Moroder, Hans-Jürgen Musiol
Mar 18, 2020·Future Medicinal Chemistry·Florence M BrunelRichard D DiMarchi
Mar 21, 2020·Chemistry : a European Journal·Mads ØstergaardKnud J Jensen
Feb 1, 1979·International Journal of Peptide and Protein Research·R C Paynovich, F H Carpenter
Aug 1, 1983·International Journal of Peptide and Protein Research·B R Srinivasa, F H Carpenter

Related Concepts

Fat Pad
Cyanogen Bromide
Hydrogen-Ion Concentration
Insulin B Chain
Infrared Spectrophotometry
Spectrophotometry, Ultraviolet
Structure-Activity Relationship

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

The Tendon Seed Network

Tendons are rich in the extracellular matrix and are abundant throughout the body providing essential roles including structure and mobility. The transcriptome of tendons is being compiled to understand the micro-anatomical functioning of tendons. Discover the latest research pertaining to the Tendon Seed Network here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.


Incretins are metabolic hormones that stimulate a decrease in glucose levels in the blood and they have been implicated in glycemic regulation in the remission phase of type 1 diabetes. Here is the latest research.

Chromatin Regulation and Circadian Clocks

The circadian clock plays an important role in regulating transcriptional dynamics through changes in chromatin folding and remodelling. Discover the latest research on Chromatin Regulation and Circadian Clocks here.

Long COVID-19

“Long Covid-19” describes illness in patients who are reporting long-lasting effects of the SARS-CoV-19 infection, often long after they have recovered from acute Covid-19. Ongoing health issues often reported include low exercise tolerance and breathing difficulties, chronic tiredness, and mental health problems such as post-traumatic stress disorder and depression. This feed follows the latest research into Long Covid.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.