Insulin synthetic analogues

To close this section, we briefly mention that reactions of deamidation are not restricted to oligopeptides, as might be deduced from the above examples. For example, pramlintide (Fig. 6.20), a synthetic analogue of human amylin, is a hormone that acts as a partner to insulin in controlling blood glu-... 

Fig. 6.2 Biological effects of IPG from different sources on otic vesicle and cochleovestib-ular ganglion. (A) Purified IPG mimicked the effects of IGF-I on Jun expression and could be involved in the mechanism that triggers proliferation in response to insulin and IGF-I during early organogenesis of the avian inner ear. C3, synthetic analogue of IPG a-IPG, anti-IPG antibody. Scale bar, 125 pm. Reprinted with permission from Ref. [11] ...

Pramlintide is a synthetic analogue of amylin, a pancreatic hormone involved in glucose homoeostasis. It slows the rate of gastric emptying and reduces appetite. It is given subcutaneously immediately prior to meals, and is used in patients already receiving insulin. 

Thevis, M., Thomas, A., Delahaut, P., Bosseloir, A. and Schanzer, W., Quahtative determination of synthetic analogues of insulin in human plasma by immunoaffinity purification and liquid chromatography-tandem mass spectrometry for doping control purposes. Anal. Chem., 77(11), 3579-3585 (2005). 

Octreotide -synthetic peptide analogue of somatostatin -abdominal pain, nausea, vomiting, diarrhea -local injection site reactions -cholelithiasis -sweating, flushing -hyperglycemia (many patients will require insulin therapy)... 

Octreotide acetate (Sandostatin) is a synthetic peptide analogue of the hormone somatostatin. Its actions include inhibition of the pituitary secretion of growth hormone and an inhibition of pancreatic islet cell secretion of insulin and glucagon. Unlike somatostatin, which has a plasma half-life of a few minutes, octreotide has a plasma elimination half-Hfe of 1 to 2 hours. Excretion of the drug is primarily renal. 

The first synthesis reported by Merrifield produced the desired tetrapeptide (Leu-Ala-Gly-Val).f l Amino acids, dipeptides, and tripeptides were all detected in the crude product released from the resin. Through continued improvements of the method, the high speed of the amino acid incorporation and automation, the solid-phase peptide synthetic methodology has become the method of choice for most laboratories synthesizing peptides. Shortly after the introduction of the solid-phase procedure it was used to synthesize insulin. This impressive achievement awakened the biochemical community to the promise of synthetic chemistry and initiated a period in which large numbers of peptide analogues were prepared and analyzed. 

In the treatment of diseases where the metabolites are not being delivered to the system, synthetic metabolites or active analogues have been successfully administered. Vitamin D3 metabolites have been successfully used for treatment of milk fever in catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy in humans. Many of these clinical studies are outlined in References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamly of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated in the intestine, kidney, and bone, the metabolite acts on the immune system, p-cells of the pancreas (insulin secretion), cerebellum, and hypothalamus. 

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