High throughput methodology for library synthesis and encoding/sequencing /
A photocleavable linker was designed and synthesized. The "photolytic mass laddering" technique featuring this linker and MALDI-TOF mass spectrometry was developed. Experiments on model peptides demonstrated this method is an efficient, sensitive and reliable approach for sequence determ...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
2000.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=727853551&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | A photocleavable linker was designed and synthesized. The "photolytic mass laddering" technique featuring this linker and MALDI-TOF mass spectrometry was developed. Experiments on model peptides demonstrated this method is an efficient, sensitive and reliable approach for sequence determination of peptides generated via split synthesis. Photolytic mass laddering has some advantages over other mass spectrometry based methodologies developed for the same purpose. A variety of intramolecular nucleophilic aromatic substitution (S[]Ar) reaction conditions were tested on a 16-membered ring macrocyclization. K₂CO₃/18-crown-6 in DMF turned out to be the optimal set of conditions. This mild reaction facilitated formations of 13- to 19-membered cyclic peptidomimetics on Rink's amide resin. Neurotrophin-3 (NT-3) β-turn mimics have attracted great interest in drug discovery and clinical research. A number of NT-3 β-turn mimics generated with efficient solid phase S[]Ar macrocyclization have shown weak activities in receptor binding assays. Two groups of bivalent ligands were prepared by tethering two units of 14- and 15-membered β-turn mimics using the "reactions of libraries with libraries" concept. Three dimeric ligands demonstrated specific agonistic activity to TrkC receptor in microphysiometry analysis. Synthesis of a C-O-D-O-E ring analog of vancomycin aglycon on solid support was attempted. An N-BOC removal method on an acid labile solid support using trimethylsilyl triflate (TMSOTf) and 2,6-lutidine was developed. The linear hexapeptide precursor was assembled on TentaGel RAM resin using this novel BOC deproection protocol. A simultaneous S[]Ar bismacrocyclization yielded an inseparable mixture of atropisomers and epimers. MALDI-TOF mass spectrometry is an excellent technique for oligonucleotide and nucleoside triphosphate analyses. Quality of the mass spectra was greatly improved by using 2,4,6-trihydroxyacetophenone as the matrix and diammonium citrate as an additive. Substituting A or G with synthesized analog 1-(2'-deoxy-β-D-ribofuranosyl)-3-nitropyrrole could partially reduce fragmentation. |
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| Item Description: | Vita. "Major Subject: Chemistry". |
| Physical Description: | xiv, 221 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 107-119). |