Synthesis of human

It is often important to control the CSD of pharmaceutical compounds, eg, in the synthesis of human insulin, which is made by recombinant DNA techniques (1). The most favored size distribution is one that is monodisperse, ie, all crystals are of the same size, so that the rate at which the crystals dissolve and are taken up by the body is known and reproducible. Such uniformity can be achieved by screening or otherwise separating the desired size from a broader distribution or by devising a crystallization process that will produce insulin in the desired form. The latter of these options is preferable, and considerable effort has been expended in that regard. 

These steps can be repeated to add one amino acid at a time to the growing chain or to link two peptide chains together. Many remarkable achievements in peptide synthesis have been reported, including a complete synthesis of human insulin. Insulin is composed of two chains totaling 51 amino acids linked by two disulfide bridges. Its structure was determined by Frederick Sanger, who received the 1958 Nobel Prize in chemistry for his work. 

P Sieber, B Kamber, J Hartmann, A Johl, B Riniker, W Rittel. 4. Total synthesis of human insulin. IV Description of the final product. Helv Chim Acta 60, 27, 1977. 

E Atherton, M Caviezel, H Fox, D Harkiss, H Over, RC Sheppard. Peptide synthesis. Part 3. Comparative solid-phase synthesis of human P-endorphin on polyamide supports using t-butoxycarbonyl and fluorenylmethoxycarbonyl. 

T Kimura, M Takai, Y Masui, T Morika, S Sakakibara. Strategy for the synthesis of large peptides an application to the total synthesis of human parathyroid hormone [hPTH (1-84)]. Biopolymers 20, 1823, 1981. 

K. Morihara, T. Oka, H. Tsuzuki, Semi-Synthesis of Human Insulin by Trypsin-Catalyzed Replacement of AlaB30 by Thr in Porcine Insulin , Nature 1979, 280, 412-413. 

Once the desired gene (such as the one that directs the synthesis of human insulin) has been located, some mechanism must be found for inserting it into the host animal (the bacterium, cow, pig. 

Idoxuridine and congeners are incorporated into DNA with deleterious results. This also applies to the synthesis of human DNA. Therefore, idoxuridine and analogues are suitable only for topical use (e.g., in herpes simplex keratitis). 

Typically, 7.0 g of human insulin can be prepared from 10 g of purified porcine insulin. The process allows large-scale production of human insulin simply and inexpensively. The complete de novo synthesis of human insulin, while technically possible, is economically unattractive. 

Scheme 5 Total Synthesis of Human Insulin by Selective Formation of Disulfides at Different Stages of a Fragment Condensation Scheme 1... 

Scheme 12 The Fragment Synthesis of Human Midkine in Homogeneous Solution in a Mixture of Chloroform and Trifluoroethanoll44 Boc—(1-11) —OPac I Boc—(12-22)—OPac II Boc—(23-31)—OPac III Boc—(32-40)—OPac IV Boc—(41-51)—OPac V Boc—(52-59)—OPac VI...

Scheme 9 Structure of Segments Designed for the Synthesis of Human Midkine 61...

Table 4 Analytical Data for the Protected Segments Used for the Synthesis of Human Midkine3...

Scheme 12 Final Steps for the Synthesis of Human Midkinel61...

Synthesis of Human Brain Natriuretic Peptide (hBNP) 951... 

Scheme 21 Synthesis of Human Insulin by the Fragment Condensation Strategy in Solution1184183 ...

Scheme 24 Synthesis of Human Insulin by Regioselective Disulfide Bridging of the A- and B-Chains1 1 31...

Proteins from animal sources Proteins from animal sources (meat, poultry, milk, fish) have a high quality because they contain all the essential amino acids in proportions similar to those required for synthesis of human tissue proteins (Figure 27.18). [Note Gelatin prepared from animal collagen is an exception it has a low biologic value as a result of deficiencies in several essential amino acids.]... 

Scheme 22. Synthesis of human rhinovirus 3C protease inhibitors.

Ochiai, H., Park, H.M., Nakamura, A., Sasaki, R., Okumura, J.I. and Muramatsu, T. (1998) Synthesis of human erythropoietin in vivo in the oviduct of laying hens by localized in vivo gene transfer using electroporation. Poult. Sci., 77, 299-302. 

Strutz F, Heeg M, Kochsiek T, Siemers G, Zeisberg M, Muller GA. Effects of pentoxifylline, pentifylline and gamma-interferon on proliferation, differentiation, and matrix synthesis of human renal fibroblasts. Nephrology Dialysis Transplantation 2000, 15, 1535-1546. 

Many preparations are available for the treatment of diabetics with insulin. Rittel et al.128) described total synthesis of human insulin in 1974. Since that time new ways of obtaining insulin have been developed, namely the E. Lilly Co. biotechnological synthesis by genetically modified microorganisms l29) (DNA recombination)... 

Weimann BI and Hermann D (1999) Studies on wound healing effects of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts in culture. International Journal of Vitamin and Nutrition Research 69, 113-19. 

Hackeng, T. M., Rosing, J., Spronk, H. M. H., and Vermeer, C. (2001) Total chemical synthesis of human matrix Gla protein. Protein Science 10, 864-870. 

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