eprintid: 8309 rev_number: 4 userid: 6 dir: disk0/00/00/83/09 datestamp: 2011-11-10 19:50:32 lastmod: 2016-11-15 13:45:35 status_changed: 2011-11-10 19:50:32 type: thesis_degree metadata_visibility: show contact_email: sharadg2003@gmail.com item_issues_count: 0 eprint_status: archive creators_name: Gupta, Sharad creators_email: sharadg2003@gmail.com title: Expanding the complexity and functional diversity of bis-amino acid building blocks ispublished: unpub divisions: sch_as_chemistry full_text_status: public keywords: bis-amino acids; diketopiperazine; foldamers; peptides abstract: We are developing a unique approach to the synthesis of macromolecules with programmable shape. These scaffolds are assembled from stereochemically pure orthogonally protected bis-amino acids that are interconnected by two amide bonds. This ladder-like arrangement restricts the conformational flexibility of bis-amino acids to a large extent which in turn drastically reduces the number of allowed conformations for an oligomer. As a result, significantly lesser computing power is needed for the final three-dimensional structure prediction. Several stereochemically pure bis-amino acid monomers have been synthesized by our research group and incorporated into a number of homo- and hetero-oligomers.In this dissertation we present the synthesis of a new pipecolic acid-based bis-amino acid building block pip5(2S5S). Assembly of this monomer into a short spiroladder oligomer utilizing solid-phase synthesis followed by in situ activation by dicyclohexylcarbodiimide and N-hydroxysuccinimide has been demonstrated. The structure of the oligomer was determined in aqueous solution using two-dimensional NMR. We report improved conditions for rapidly and simultaneously closing multiple diketopiperazines on solid support. These new conditions involve either heating of a suspension of solid supported amino-tetrafluoropropyl esters in acetic acid/triethylamine catalyst solution in a microwave oven or continuous flow of catalyst solution through the resin, heated in a special flow cell apparatus.Finally, the synthesis of the first functionalized bis-amino acid monomer proAc(2S3S4R) that carries an acetyl side chain is presented. This monomer was incorporated into a short oligomer and the solution phase structure was determined using two-dimensional nuclear magnetic resonance. The solution structure confirmed the intended connectivity and stereochemistry of the oligomer. This first functionalized bis-amino acid represents a milestone towards functionalized bis-peptide nanostructures for catalytic, molecular recognition and nanotechnology applications. date: 2009-09-30 date_type: completed institution: University of Pittsburgh refereed: TRUE etdcommittee_type: committee_chair etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_name: Schafmeister, Christian E etdcommittee_name: Wilcox, Craig S etdcommittee_name: Das, Subha R etdcommittee_name: Chapman, Toby etdcommittee_email: meister@temple.edu etdcommittee_email: daylite@pitt.edu etdcommittee_email: srdas@andrew.cmu.edu etdcommittee_email: tchapman@pitt.edu etdcommittee_id: etdcommittee_id: DAYLITE etdcommittee_id: etdcommittee_id: TCHAPMAN etd_defense_date: 2009-07-13 etd_approval_date: 2009-09-30 etd_submission_date: 2009-07-08 etd_access_restriction: immediate etd_patent_pending: FALSE assigned_doi: doi:10.5195/pitt.etd.2011.8309 thesis_type: dissertation degree: PhD committee: Christian E. Schafmeister (meister@temple.edu) - Committee Chair committee: Craig S. Wilcox (daylite@pitt.edu) - Committee Member committee: Subha R. Das (srdas@andrew.cmu.edu) - Committee Member committee: Toby Chapman (tchapman@pitt.edu) - Committee Member etdurn: etd-07082009-204223 other_id: http://etd.library.pitt.edu/ETD/available/etd-07082009-204223/ other_id: etd-07082009-204223 citation: Gupta, Sharad (2009) Expanding the complexity and functional diversity of bis-amino acid building blocks. Doctoral Dissertation, University of Pittsburgh. (Unpublished) document_url: http://d-scholarship-dev.library.pitt.edu/8309/1/Sharad_Gupta_2009.pdf