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Synthesis and evaluation of the biological activity of analogues of pepstatin
dc.contributor.advisor | Glover, G. I. | |
dc.creator | Liu, Wu-Schyong | |
dc.date.accessioned | 2020-08-21T22:12:52Z | |
dc.date.available | 2020-08-21T22:12:52Z | |
dc.date.issued | 1980 | |
dc.identifier.uri | https://hdl.handle.net/1969.1/DISSERTATIONS-685152 | |
dc.description | Vita. | en |
dc.description.abstract | Synthesis of all four stereoisomers of the novel amino acid statine, 4-amino-3-hydroxy-6-methylhepatanoic acid, and alastatine, 4-amino-3-hydroxypentanoic acid has been accomplished. Several tripeptide analogues of pepstatin have been prepared and tested as inhibitors of pepsin and cathepsin D in vitro. N-Carbobenzoxy-L-valyl-L-valyl-(3S,4S)-statine, 22a, was 20-fold less effective than pepstatin. The analogue of 22a in which the (3S,4S)-statine was replaced by (3R,4S)-statine showed a 210-fold decrease in activity, whereas the replacement of (3S,4R)-statine resulted in 2240-fold decrease. These results indicate that the stereochemistry of statine is important for the biological activity of the peptides. The S-configuration at both the 3 and 4 positions is required for tight binding to the enzyme. The antipepsin activity of the tripeptide containing (3S,4S)-alastatine was 168 times weaker than that of tripeptide 22a, while as a cathepsin D inhibitor the former tripeptide was 875 times less effective than the latter tripeptide. These data suggest that the side chain of the novel amino acid plays a significant role in the biological action of the peptide inhibitors. | en |
dc.format.extent | ix, 64 leaves | en |
dc.format.medium | electronic | en |
dc.format.mimetype | application/pdf | |
dc.language.iso | eng | |
dc.rights | This thesis was part of a retrospective digitization project authorized by the Texas A&M University Libraries. Copyright remains vested with the author(s). It is the user's responsibility to secure permission from the copyright holder(s) for re-use of the work beyond the provision of Fair Use. | en |
dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | |
dc.subject | Major chemistry | en |
dc.subject.classification | 1980 Dissertation L783 | |
dc.subject.lcsh | Peptides | en |
dc.subject.lcsh | Chemical inhibitors | en |
dc.subject.lcsh | Proteins | en |
dc.subject.lcsh | Synthesis | en |
dc.title | Synthesis and evaluation of the biological activity of analogues of pepstatin | en |
dc.type | Thesis | en |
thesis.degree.grantor | Texas A&M University | en |
thesis.degree.name | Doctor of Philosophy | en |
dc.contributor.committeeMember | Hogg, John L. | |
dc.contributor.committeeMember | Magill, Jane M. | |
dc.type.genre | dissertations | en |
dc.type.material | text | en |
dc.format.digitalOrigin | reformatted digital | en |
dc.publisher.digital | Texas A&M University. Libraries | |
dc.identifier.oclc | 6874729 |
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