DL-2-Amino-4-phosphonobutyric acid, an isostere of phosphoserine, was incorporated into the heptapeptide sequence, Leu-Arg-Arg-Ala-(DL-2-amino-4-phosphonobutyric acid)-Leu-Gly, for kinetic mechanistic studies of the cAMP-dependent protein kinase. To block the phosphono hydroxyl groups, methyl, ethyl and 4nitrobenzyl esters were studied as possible protecting groups. The phosphono diethyl ester of the N-Fmoc-protected amino acid was utilized in the synthesis of the heptapeptide. Two configurational forms of the protected peptide were obtained and were separated by C18-reverse phase HPLC. Characterization of the two isomeric forms was accomplished by 3 1P NMR, 1H NMR, 13C% NMR and amino acid analysis. The protecting groups of the isomeric phsophonopeptides were removed by HBr/AcOH and purified by cation exchange HPLC. Both phosphonopeptides were found to be inhibitors of the cAMP-dependent protein kinase, having Ki values of 0.6 mM (peptide A) and 1.9 mM (peptide B).
| Identifer | oai:union.ndltd.org:unt.edu/info:ark/67531/metadc500671 |
| Date | 12 1900 |
| Creators | Yang, Chunhua |
| Contributors | Norton, Scott, Cook, Paul F., Wu, Edward Ming-chi, 1938- |
| Publisher | University of North Texas |
| Source Sets | University of North Texas |
| Language | English |
| Detected Language | English |
| Type | Thesis or Dissertation |
| Format | v, 59 leaves : ill., Text |
| Rights | Public, Copyright, Copyright is held by the author, unless otherwise noted. All rights reserved, Yang, Chunhua |
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