The Bakerian Lecture Towards synthesis of proteins

The Royal Society - Tập 353 Số 1675 - Trang 441-457 - 1977
G. W. Kenner1
1The Robert Robinson Laboratories, University of Liverpool, Liverpool L69 3BX

Tóm tắt

Proteins, as their name indicates, occupy the prime place in Nature’s architecture. It is worth remarking that Nature uses the structural type for diverse purposes, in addition to those familiar in enzymology, immunology, etc. A striking example is provided by the recent publication (Bradbury et al . 1976), showing that the C fragment of lipotropin (residues 61-91) is firmly bound by opiate receptors and is an analgesic 200 times as potent as morphine in molar terms. The pentapeptide comprising residues 61-65 of this sequence is already well known as enkephalin (Hughes et al . 1975). Reference should also be made to the host of hormones from the pituitary gland, hypothalamus, and intestinal tract. An example of the last is gastrin which has been studied at Liverpool, principally by R. A. Gregory in the Department of Physiology. Recently the structure of the big gastrins, isolated by Gregory & Tracy (1972), has been elucidated by Harris & Runswick (1974) following preliminary work in the Robert Robinson Laboratories (Barton, Choud- hury, Dancsi & Kenner 1973) (figure 1). This structure typifies the way in which small fragments are carved from a protein chain in order to provide an active hormone (Smyth 1975). Thus the gastrins originally described (Gregory & Tracy 1964; Kenner & Sheppard 1968) correspond to the sequence 18-34 of the big gastrins. The lysyl glutaminyl bond is enzymically cleaved, as can be achieved in the laboratory by trypsin, and then the N-terminal glutaminyl residue cyclizes to the pyroglutamyl structure (pyrrolidone carbonyl). The pyroglutamyl structure at the N-terminus of the big gastrins must have arisen in the same way. It should also be noted that the C-terminal amide, which is essential for biological activity (Tracy & Gregory 1964), very likely arises from enzymatic aminolysis of a protein chain extending further to the right; the extensive studies by Morley (1968) of structure- activity relations in the gastrin tetrapeptide indicate that the gastrin tetrapeptide embedded in a protein chain would not have hormonal activity until aminolysis had occurred, and therefore the gastrin sequence can be stored in a prohormone. The sequence of human big gastrin 1 (figure 1) has been synthesized by a colla­borative effort between our laboratory at Liverpool and that of Professor E. Wünsch in the Max Planck Institute at Munich (Choudhury et al . 1976).

Từ khóa


Tài liệu tham khảo

Albertson N. F. 1962 Org. Reactions12 202-355.

10.1038/204933a0

Andreatta R. H., 1973, Helv. chim, Acta, 56, 1205

Arshady R. Kenner G. W. & Ledwith A. 1974 J. Polymer Sci. Polymer chem. ed. 12 2017-2025.

Atherton E., 1975, J. Am. chem, Soc., 97, 6584

Barton M. Choudhury A. M. Dancsi L. & Kenner G. W. 1973 unpublished work.

Bates A. J., 1975, Helv. chim, Acta., 58, 688

Beacham J., 1971, J. Am. chem, Soc., 93, 5526

Bergmann M. & Zervas L. 1932 Ber.65 1192-1201.

10.1038/newbio232012a0

10.1038/260793a0

Camble R., 1969, J. chem, Soc. (C), 1911

10.1038/newbio232016a0

Castro B. Dormoy J. R. Evin G. & Selve C. 1975 Tetrahedron Letters 1219-1222.

Chipman D. M. & Sharon N. 1969 Science N .Y . 165 454-465.

Choudhury A. M. Kenner G. W. Moore S. Ramage R. Richards P. M. Thorpe W. D. Moroder L. Wendlberger G. & Wiinsch E. 1976 Proceedings IRh European Peptide Symposium (In the Press.)

10.1039/jr9570001398

Denkewalter R. G., 1969, J . Am. chem, Soc., 91, 502

10.1038/247202a0

10.1016/S0021-9673(01)81054-2

10.1016/S0021-9673(00)81122-X

Goldberger R. F., 1963, J. biol, Chem., 238, 2988

Gregory R. A. & Tracy H. J. 1964 Gut 5 103-114.

Gregory R. A., 1972, Lancet, 797-799. Gutte, B. & Merrifield, R. B. 1969 Gutte, B. & Merrifield, R. B. 1971 J . A m .chem. 91, 501-502. J .biol, Chem., 246, 1922

Haas W. L., 1966, J . Am. chem, Soc., 88, 1988

Haque M. & Caughlan C. N. 1966 J. chem. Soc. Chem. Comm. 921.

Hirschmann R., 1969, J . Am. chem, Soc., 91, 507

Hudson D. Kenner G. W. Mason B. Morgan B. Ramage R. Singh B. & Tyson R. 1973 Proceedings 12th European Peptide Symposium 70-71. Amsterdam: North-Holland Publishing.

Hudson D. 1973 Research report the Robert Robinson Laboratories Liverpool.

10.1038/258577a0

Ivanov V. T. Mikhaleva I. I. Volpina O. M. Myagkova M. A. & Deigin V. I. 1976 Proc. 14 thEuropean Peptide Symposium (In the Press.)

Jackson A. G. Kenner G. W. Moore G. A. Ramage R. & Thorpe W. D. 1976 Tetrahedron Letters 3627-3630.

Jenkins S. R., 1969, J. Am. chem, Soc., 91, 505

Johnson L. N. Phillips D. C. & Rupley J. A. 1968 Structure function and evolution in proteins. Brookhaven symposia in biology no. 21 120-136.

Kawasaki K., 1973, J • Am. chem, Soc., 95, 6815

Kenner G. W. Moore G. A. & Ramage R. 1976 Tetrahedron Letters 3623-3626.

10.1098/rspb.1968.0027

Kenner G. W., 1972, J ■Am. chem, Soc., 94, 3259

Kenner G. W. 1951 Chem. and Ind. 15.

10.1039/jr9520002069

10.1021/cr60165a001

10.1002/cber.19701030319

Meienhofer J. 1973 Hormonal proteins and peptides vol. 2 ch. 3 pp. 48-267. New York: Academic Press.

Merrifield R. B., 1963, J . Am. chem, Soc., 85, 2149

10.1098/rspb.1968.0028

Moroder L. Borin G. F. Marchiori F. & Scoffone E. 1973 Biopolymers 12 477-492.

Moroder L. Marchiori F. Borin G..& Scoffone E. 1973 Biopolymers 12 729-750.

Mummery A. F. 1936 M y climbs in the Alps and Caucasus ch. 6. Oxford: Basil Blackwell.

Mutter M. Hagenmaier H. & Bayer E. 1971 Angew. chemie inti. ed. 10 811-812.

Ondetti M. A. Deer A. Sheehan J. T. Pluscec J. & Kocy O. 1968 Biochem. 7 4069-4075.

Pinker T. G., 1976, J. chem, Soc. Perlcin Trans., 220

Riniker B., 1975, Helv. chim, Acta, 58, 1086

Saxena V. P. & Wetlaufer D. B. 1970 Biochem. 9 5015-5023.

Schwyzer R., 1963, Helv. chim, Acta, 46, 1975

Schwyzer R., 1963, Helv. chim, Acta, 46, 1550

Schwyzer R., 1955, Helv. chim, Acta, 38, 80

Schwyzer R., 1955, Helv. chim, Acta, 38, 83

Sharp J. J., 1973, J . Am. chem, Soc., 95, 6097

Sheehan J. C., 1955, J. Am. chem, Soc., 77, 1067

Sieber P., 1974, Helv. chim, Acta, 57, 2617

Sieber P. & Iselin B. 1968 Helv. chim. Acta51 622-632.

Smyth D. G. 1975 Nature Lond. 257 89-90. See also 1975 Polypeptide hormones: molecular and cellular aspects. CIBA Foundation Symposium no. 41 (new series) Amsterdam: Elsevier.

Stelzel P. & Wendlberger G. 1974 Ch. 41 in Methoden der Chemie (Houben-Weyl) vol. 15. Stuttgart: Georg Thieme Verlag.

Storey H. T., 1972, J. Am.chem, Soc., 94, 6170

Strachan R. G., 1969, J. Am. chem, Soc., 91, 503

10.1038/204935a0

Veber D. F., 1975, Peptides: chemistry, structure, and biology. Proc. 4th Am, Peptide Symp., 307

Veber D. F., 1972, J . Am. chem, Soc., 94, 5456

10.1515/znb-1966-0507

Wiinsch E. 1971 Angew. chem. internat. edit. 10 786-795.

10.1002/cber.19660990119

Yamashiro D., 1973, J. Am. chem, Soc., 95, 1310

Thông tin
Thông tin xuất bản

The Royal Society

Tập 353 Số 1675

441-457

Thông tin tác giả