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The ribosome is a ribozyme and central to the biosynthesis of proteins in all organisms. It has a strong bias against non-alpha-L-amino acids, such as alpha-D-amino acids and beta-amino acids. Additionally, the ribosome is only able to incorporate one amino acid in response to one codon. It has been demonstrated

The ribosome is a ribozyme and central to the biosynthesis of proteins in all organisms. It has a strong bias against non-alpha-L-amino acids, such as alpha-D-amino acids and beta-amino acids. Additionally, the ribosome is only able to incorporate one amino acid in response to one codon. It has been demonstrated that reengineering of the peptidyltransferase center (PTC) of the ribosome enabled the incorporation of both alpha-D-amino acids and beta-amino acids into full length protein. Described in Chapter 2 are five modified ribosomes having modifications in the peptidyltrasnferase center in the 23S rRNA. These modified ribosomes successfully incorporated five different beta-amino acids (2.1 - 2.5) into E. coli dihydrofolate reductase (DHFR). The second project (Chapter 3) focused on the study of the modified ribosomes facilitating the incorporation of the dipeptide glycylphenylalanine (3.25) and fluorescent dipeptidomimetic 3.26 into DHFR. These ribosomes also had modifications in the peptidyltransferase center in the 23S rRNA of the 50S ribosomal subunit. The modified DHFRs having beta-amino acids 2.3 and 2.5, dipeptide glycylphenylalanine (3.25) and dipeptidomimetic 3.26 were successfully characterized by the MALDI-MS analysis of the peptide fragments produced by "in-gel" trypsin digestion of the modified proteins. The fluorescent spectra of the dipeptidomimetic 3.26 and modified DHFR having fluorescent dipeptidomimetic 3.26 were also measured. The type I and II DNA topoisomerases have been firmly established as effective molecular targets for many antitumor drugs. A "classical" topoisomerase I or II poison acts by misaligning the free hydroxyl group of the sugar moiety of DNA and preventing the reverse transesterfication reaction to religate DNA. There have been only two classes of compounds, saintopin and topopyrones, reported as dual topoisomerase I and II poisons. Chapter 4 describes the synthesis and biological evaluation of topopyrones. Compound 4.10, employed at 20 µM, was as efficient as 0.5 uM camptothecin, a potent topoisomerase I poison, in stabilizing the covalent binary complex (~30%). When compared with a known topoisomerase II poison, etoposide (at 0.5 uM), topopyorone 4.10 produced similar levels of stabilized DNA-enzyme binary complex (~34%) at 5 uM concentration.
ContributorsMaini, Rumit (Author) / Hecht, Sidney M. (Thesis advisor) / Gould, Ian (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2013
ContributorsEvans, Bartlett R. (Conductor) / Schildkret, David (Conductor) / Glenn, Erica (Conductor) / Concert Choir (Performer) / Chamber Singers (Performer) / ASU Library. Music Library (Publisher)
Created2018-03-16
ContributorsOwen, Ken (Conductor) / McDevitt, Mandy L. M. (Performer) / Larson, Brook (Conductor) / Wang, Lin-Yu (Performer) / Jacobs, Todd (Performer) / Morehouse, Daniel (Performer) / Magers, Kristen (Performer) / DeGrow, Gary (Performer) / DeGrow, Richard (Performer) / Women's Chorus (Performer) / Sun Devil Singers (Performer) / ASU Library. Music Library (Publisher)
Created2004-03-24
ContributorsMetz, John (Performer) / Sowers, Richard (Performer) / Collegium Musicum (Performer) / ASU Library. Music Library (Publisher)
Created1983-01-29
ContributorsEvans, Bartlett R. (Conductor) / Glenn, Erica (Conductor) / Steiner, Kieran (Conductor) / Thompson, Jason D. (Conductor) / Arizona Statesmen (Performer) / Women's Chorus (Performer) / Concert Choir (Performer) / Gospel Choir (Conductor) / ASU Library. Music Library (Publisher)
Created2019-03-15
ContributorsKillian, George W. (Performer) / Killian, Joni (Performer) / Vocal Jazz Ensemble (Performer) / ASU Library. Music Library (Publisher)
Created1992-11-05
ContributorsButler, Robb (Conductor) / McCreary, Kimilee (Conductor) / Bakko, Nicki L. (Conductor) / Schreuder, Joel (Conductor) / Larson, Matthew (Performer) / Ortman, Mory (Performer) / Graduate Chorale I (Performer) / Graduate Chorale II (Performer) / ASU Library. Music Library (Publisher)
Created1999-12-02
ContributorsGarrett, Jennifer (Conductor) / FitzPatrick, Carole (Performer) / Aspnes, Lynne (Performer) / Campbell, Andrew (Pianist) (Performer) / Ryan, Russell (Performer) / Rockmaker, Jody (Performer) / Kocour, Mike (Performer) / McLin, Katherine (Performer) / Larson, Brook Carter (Conductor) / Women's Chorus (Performer) / Men's Chorus (Performer) / ASU Library. Music Library (Publisher)
Created2009-05-04
ContributorsLarson, Brook Carter (Conductor) / Gentry, Gregory R. (Conductor) / Garrison, Ryan D. (Conductor) / Schildkret, David (Conductor) / Men's Chorus (Performer) / Symphonic Chorale (Performer) / Women's Chorus (Performer) / Chamber Singers (Performer) / Choral Union (Performer) / ASU Library. Music Library (Publisher)
Created2007-12-03
ContributorsHerberger Singers (Performer) / Sun Devil Singers (Performer) / ASU Library. Music Library (Publisher)
Created2004-10-24