Abstract
1. At 30min after oral administration unchanged Synacthen [corticotrophin-(1–24)-tetracosapeptide] was found in the stomach but could not be detected in the lumen of the small intestine of the rat. 2. Synacthen and 41795-Ba {[d-Ser1, Lys17, Lys18]corticotrophin-(1–18)-octadecapeptide amide} were rapidly metabolized in vitro by both intestinal juice and everted pieces of small intestine. Peptide products were not found either in the intestinal tissue or in the fluid bathing the serosal tissue. 3. Glucose but not O2 was necessary for the breakdown of the two adrenocorticotrophin analogues by everted tissue. 4. When the products obtained after partial digestion were chromatographically separated and identified, a pattern of breakdown emerged. The N-terminus of Synacthen and the Phe(7)–Arg(8) bond in both analogues were particularly labile. The d-serine N-terminal residue of 41795-Ba conferred a marked protection to aminopeptidase action. 5. The relative susceptibilities of peptide bonds would have been difficult to predict on the basis of existing knowledge of the properties of enzymes of the small intestine.
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- Edelhoch H. Spectroscopic determination of tryptophan and tyrosine in proteins. Biochemistry. 1967 Jul;6(7):1948–1954. doi: 10.1021/bi00859a010. [DOI] [PubMed] [Google Scholar]
- Fern E. B., Hider R. C., London D. R. The sites of hydrolysis of dipeptides containing leucine and glycine by rat jejunum in vitro. Biochem J. 1969 Oct;114(4):855–861. doi: 10.1042/bj1140855. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lowry P. J., Chadwick A. Purification and amino acid sequence of melanocyte-stimulating hormone from the dogfish Squalus acanthias. Biochem J. 1970 Aug;118(5):713–718. doi: 10.1042/bj1180713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MAY A. J., WHALER B. C. The absorption of Clostridium botulinum type A toxin from the alimentary canal. Br J Exp Pathol. 1958 Jun;39(3):307–316. [PMC free article] [PubMed] [Google Scholar]
- Matthews D. M., Lis M. T., Cheng B., Crampton R. F. Observations on the intestinal absorption of some oligopeptides of methionine and glycine in the rat. Clin Sci. 1969 Dec;37(3):751–764. [PubMed] [Google Scholar]
- McMartin C., Simpson P., Thorpe N. The specific assay of basic drugs in urine by CM-cellulose chromatography using continuous drug-dye complex extraction as a detection system. J Chromatogr. 1969 Aug 5;43(1):72–83. doi: 10.1016/s0021-9673(00)99168-4. [DOI] [PubMed] [Google Scholar]
- PORATH J. Use of triethlammonium buffers in ion-exchange chromatography and electrophoresis. Nature. 1955 Mar 12;175(4454):478–478. doi: 10.1038/175478a0. [DOI] [PubMed] [Google Scholar]