Synthetic insulins

Insulin is available as purified extracts from beef and pork pancreas and is biologically similar to human insulin. However, these animal source insulins are used less frequently today than in years past. They are being replaced by synthetic insulins, including human insulin or insulin analogy. 

Science and civilisation in China. Volume 5. Chemistry and chemical technology. Part HI Spagyrical discovery and invention Historical survey, from cinnebar elixirs to synthetic insulin, by Joseph Needham, Ho Ping-Yu, Lu Gwei-Djen and Nathan Sivin. Cambridge Cambridge Univ P, 1976. 

Attempts to prepare synthetic insulin repeatedly encountered the... 

We shall prepare the various building blocks of the catalyst surface and study them separately. Then we put the parts together and the resultant structure should have all of the properties of the working catalyst particle. Just as in the case of synthetic insulin or the B12 molecule, the proof that the synthesis was successful is in the identical performance of the synthesized and natural products. Our building blocks are crystal surfaces with well-characterized atomic surface structure and composition. Cutting these crystals in various directions permits us to vary their surface structure systematically and to study the chemical reactivity associated with each surface structure. If we do it properly, all of the surface sites and microstructures with unique chemical activity can be identified this way. Then, by preparing a surface where all of these sites are simultaneously present in the correct configurations and concentrations the chemical behavior of the catalyst particle can be reproduced. The real value of this synthetic approach is that ultimately one should be able to synthesize a catalyst that is much more selective since we build into it only the desirable active sites in a controlled manner. 

Allergic reactions to insulin were originally thought to be caused by impurities present in the formulation. However, after the introduction of monocomponent insulins and human synthetic insulins, these reactions continued to be seen, even in patients without a history of treatment with other insulins (142). Switching from animal to human insulin can paradoxically cause allergic reactions, which subside when treatment with animal insulin is re-introduced... 

Insulin aspart is a rapid-acting synthetic insulin in which proline is replaced by aspartate at position 28 in the B chain. Insulin aspart has been reviewed (1). Its adverse effects do not differ from those of soluble human insulin and it has a similar effect on the blood glucose concentration (2). 

Human insulin was the first commercial health care product produced by recombinant DNA technology ZjEliJLilly,.the producer of this synthetic insulin, often relied on HPLC to confirm the structure and to determine the potency of synthetic human insulin. The story behind Lilly s recombinant DNA-produced insulin is described in an article in Science (1) High performance liquid chromatography (HPLC) techniques developed at Lilly can detect proteins that differ by a single amino acid, and HPLC tests show human insulin (recombinant DNA) is identical to pancreatic human insu-... 

The words natural and organic are quite appealing to the consumer. Synthetic is often considered less desirable. Many believe that natural is better, safer, or not foreign to the body, but quite the opposite may exist. Native is identical to what is produced by or present in the body. Natural products refers to substances that are use to promote health or treat illness derived from plant, mineral, or animal sources. Organic refers to the level of pesticides or chemicals used in the growing process. For example, insulin from pork or beef sources is natural, but not native. Recombinant insulin is synthetic, but native. Thus, synthetic, as in synthetic insulin or estrogen, does not necessarily mean foreign or less desirable. 

The switch in position of amino acids in lispro does not affect the action of this synthetic insulin on cells because it is not in a critical invariant region, but it does affect the ability of insulin to bind zinc. Normally, human insulin is secreted from the pancreas as a zinc hexa-mer in which six insulin molecules are bound to the zinc atom. When zinc insulin is injected, the binding to zinc slows the absorption from the subcutaneous (under the skin) injection site. Lispro cannot bind zinc to form a hexamer, and thus it is absorbed much more quickly than other insulins. 

The total chemical synthesis of insulin is a piece of work which stems directly from the big leap forward movement. In 1958, when the movement had attained the stage of unbounded enthusiasm for achievements, we took upon ourselves the task of making synthetic insulin as the first protein ever to be synthesized, an achievement which we hope to accomplish in a short time to serve as a contribution to the scientific progress of our mother country and also as an expression of revolutionary initiative. Kexue Tongbao, 17,241,1966)... 

Katsoyannis, P.G. Synthetic insulins. Recent Progr. Hormone Res. 23, 505-563 (1967)... 

Combination of the synthetic chains to produce insulin was originally carried out by the methods of Dixon and Du. Under these conditions, based on the starting amounts of the chains, all-synthetic insulin was produced in approximately 2 percent yield and half-synthetic insulins, consisting of one synthetic sheep or human insulin chain (A or B) and one natural bovine insulin chain, were produced in yields ranging from 4 to 8 percent. 

A most dramatic increase, however, in the yield of synthetic insulins is materialized when our method for combining insulin chains is employed (18,19). Using synthetic sheep and human insulin chains and natural bovine and porcine insulin chains, we were able... 

Isolation of the synthetic insulins from the combination mixtures of the A and B chains was originally undertaken by methods devised to isolate insulin from natural sources. We were thus able to isolate (20) synthetic insulins by applying a modified version of the method suggested by Smith (21) which, like all the existing methods of isolation, included ah acid-alcohol extraction as the initial step. The low recovery, however, of... 

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