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Synthesising insulin
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Synthesising insulin
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Views | Duration | ||
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31. Meeting Lester Smith | 212 | 01:20 | |
32. Working on vitamin B12 | 1 | 246 | 03:09 |
33. Mapping the chemical structure of B12 | 167 | 00:53 | |
34. Calculating three-dimensional electron density maps | 103 | 07:36 | |
35. Complex chemistry | 94 | 04:43 | |
36. The phase problem | 217 | 02:12 | |
37. Insulin and heavy atoms | 1 | 108 | 01:46 |
38. The Bijvoet effect | 91 | 01:50 | |
39. The structure of insulin | 677 | 04:28 | |
40. Synthesising insulin | 165 | 03:13 |
[Q] What was it, Dorothy, that you were looking for in the insulin structure?
Just what it was, you know, how the peptide chain... of course it was a very important step for us when [Fred] Sanger found the sequence. We didn't in any sense need to know it for our analysis, but it cheered us up like anything to see our distribution of atoms conforming to that expected from Sanger's sequence.
[Q] Now, when the structure came out in 1969, you, I remember very well, Dorothy, and others of us spent two days, I think, interpreting that map, and when the structure was complete we had the details really of a heximer, which I don't know what you thought about at the time, Dorothy, but it was, I think, a very beautiful structure.
Yes.
[Q] And it... in a sense, one of the first things we did was to think about Svedberg's experiments which were telling us that we had different conditions, heximers and dimers. And do you remember... can you remember looking inside this heximer for the fundamental dimer?
Yes. I'm also sort of thinking of the fact that in the... our first letters to Nature I wrote about those early measurements. I measured, of course, the molecular weight of the rhombahedral unit cell and this contained six insulin one molecules and had a molecular weight of about 36 thousand. The first suggestion was that the insulin molecule might have a weight of 36 thousand, and this led to a very irate letter from Freudenberg who was a major chemical worker on insulin at the time, saying insulin was much smaller then this, it's at least not more than 11 thousand and maybe even less, and Svedberg only measures a particle weight in his measurements in the ultra centrifuge and this was all absolutely correct and proved by the final structure analysis.
I replied politely to Freudenberg I think at the time, but I didn't see Freudenberg until really very late when I was elected a member of Leopoldina which was an academy, a very old scientific academy. It's older than the Royal Society and it was essentially an academy for all German-speaking peoples and the... to my surprise when I went to the first meeting, and I went to the Leopoldina I found that it was... there were present East and West Germans and they got away with going on meeting together in the Leopoldina all the way through this episode of the partition of Germany, and the first person I met on the steps of the Leopoldina as I was going in was Freudenberg himself and I had the structure of insulin in my hand.
British pioneer of X-ray crystallography, Dorothy Hodgkin (1910-1994), is best known for her ground-breaking discovery of the structures of penicillin, insulin and vitamin B12. At age 18, she started studying chemistry at Somerville College, Oxford, then one of the University of Oxford colleges for women only. She also studied at the University of Cambridge under John Desmond Bernal, where she became aware of the potential of X-ray crystallography to determine the structure of proteins. Together with Sydney Brenner, Jack Dunitz, Leslie Orgel, and Beryl Oughton, she was one of the first people in April 1953 to see the model of the structure of DNA, constructed by Francis Crick and James Watson. She was awarded the 1964 Nobel Prize in Chemistry and is also known for her peace work with organisations such as Science for Peace and the Medical Aid Committee for Vietnam. All recorded material copyright of The Biochemical Society.
Title: The structure of insulin
Listeners: Guy Dodson
Guy Dodson studied chemistry and physical science at the University of New Zealand, followed by a PhD on the crystallographic study of an alkaloid. In 1961, he came to Oxford to work on the crystal structure of insulin. In the mid 1970s Guy and his wife moved to York University to establish a laboratory. In addition to insulin studies the laboratory has investigated many complex molecules of medical significance, including haemoglobin, myoglobin, HIV related proteins, proteases and proteins involved in managing nucleic acids in cells. In 1993, he went to the NIMR in London to establish a crystallographic group in an environment that spanned molecular, physiological and disease-related disciplines. Here his research began on some cell signalling proteins. His interests on medically relevant proteins included prions, malarial and TB proteins, and some clinically relevant thrombin inhibitors. Guy Dodson retired in 2004 but is still finding much to do in York and the NIMR.
Tags: Leopoldina, Frederick Sanger, Rudolf Karl Freudenberg
Duration: 4 minutes, 28 seconds
Date story recorded: 1990
Date story went live: 02 June 2008