Synthesis and Kinetic Mechanism Study of Phosphonopeptide as a Dead-End Inhibitor of cAMP-Dependent Protein Kinase

PDF Version Also Available for Download.

Description

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 ... continued below

Physical Description

v, 59 leaves : ill.

Creation Information

Yang, Chunhua December 1991.

Context

This thesis is part of the collection entitled: UNT Theses and Dissertations and was provided by UNT Libraries to Digital Library, a digital repository hosted by the UNT Libraries. It has been viewed 19 times . More information about this thesis can be viewed below.

Who

People and organizations associated with either the creation of this thesis or its content.

Author

Chair

Committee Members

Publisher

Rights Holder

For guidance see Citations, Rights, Re-Use.

  • Yang, Chunhua

Provided By

UNT Libraries

With locations on the Denton campus of the University of North Texas and one in Dallas, UNT Libraries serves the school and the community by providing access to physical and online collections; The Portal to Texas History and UNT Digital Libraries; academic research, and much, much more.

Contact Us

What

Descriptive information to help identify this thesis. Follow the links below to find similar items on the Digital Library.

Degree Information

Description

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).

Physical Description

v, 59 leaves : ill.

Language

Identifier

Unique identifying numbers for this thesis in the Digital Library or other systems.

Collections

This thesis is part of the following collection of related materials.

UNT Theses and Dissertations

Theses and dissertations represent a wealth of scholarly and artistic content created by masters and doctoral students in the degree-seeking process. Some ETDs in this collection are restricted to use by the UNT community.

What responsibilities do I have when using this thesis?

When

Dates and time periods associated with this thesis.

Creation Date

  • December 1991

Added to The UNT Digital Library

  • March 9, 2015, 8:15 a.m.

Description Last Updated

  • Sept. 14, 2017, 10:58 a.m.

Usage Statistics

When was this thesis last used?

Yesterday: 0
Past 30 days: 1
Total Uses: 19

Interact With This Thesis

Here are some suggestions for what to do next.

Start Reading

PDF Version Also Available for Download.

International Image Interoperability Framework

IIF Logo

We support the IIIF Presentation API

Yang, Chunhua. Synthesis and Kinetic Mechanism Study of Phosphonopeptide as a Dead-End Inhibitor of cAMP-Dependent Protein Kinase, thesis, December 1991; Denton, Texas. (digital.library.unt.edu/ark:/67531/metadc500671/: accessed July 18, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; .