[-] Show simple item record

dc.contributor.advisorLever, Susan Z., 1952-eng
dc.contributor.authorShenoy, Nalinieng
dc.date.issued2006eng
dc.date.submitted2006 Falleng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionTitle from title screen of research.pdf file (viewed on August 8, 2007)eng
dc.descriptionVita.eng
dc.descriptionIn the 520 where natIn-DOTA ̕appears nat should be superscripted.eng
dc.descriptionIncludes bibliographical references.eng
dc.descriptionThesis (Ph. D.) University of Missouri-Columbia 2006.eng
dc.descriptionDissertations, Academic -- University of Missouri--Columbia -- Chemistry.eng
dc.description.abstractModification of the peptide sequence of DOTA-Tyr³-octreotate is carried out by substituting the cysteine moieties with D-Cysteine, L-Penicillamine and D-Penicillamine in one or both positions to study the effect of this replacement on chemical and receptor binding properties. Fmoc-solid phase peptide synthesis was used to construct the linear sequence of the peptides, including the attachment of DOTA. The cyclization of the peptides were carried out by use of [Pt(en)₂Cl₂]Cl₂ or DMSO. Steric constraints imposed by the gem-dimethyl groups on the penicillamine moieties resulted in longer reaction times and lower yields compared to the cysteine moieties. After preparative HPLC or Sep-Pak® purification, these peptides were characterized by using LCMS. nat[superscript]In-DOTA-̕peptides were synthesized and characterized by LCMS. Using ¹¹¹In, radiolabelling of these peptides was carried out. These were purified by using HPLC and the isolated radiolabelled peptide was used to carry out in vitro studies. In serum stability studies, all radiolabelled peptides were found to be stable. Preliminary results from cell uptake studies (using AR42J cell line) showed all modified peptides had lower uptakes in comparison to the control peptide, ¹¹¹In-DOTA-Tyr³-octreotate. IC₅₀ values of two peptides, nat[superscript]In-DOTA-̕ [DCys², Tyr³, DCys⁷]-octreotate and natIn-DOTA-̕[Pen², Tyr³, Pen⁷]-octreotate were in the range of 10-⁶-10-⁵ M range.eng
dc.identifier.merlinb59278286eng
dc.identifier.oclc163568319eng
dc.identifier.urihttps://hdl.handle.net/10355/4440
dc.identifier.urihttps://doi.org/10.32469/10355/4440eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.subject.lcshPeptides -- Synthesiseng
dc.subject.lcshAmino acid sequenceeng
dc.subject.lcshProteins -- Analysiseng
dc.titleInvestigation of the replacement of cysteine residues in DOTA-(Tyr³)-octreotate: synthesis, characterization and evaluation of biological activitieseng
dc.typeThesiseng
thesis.degree.disciplineChemistry (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


Files in this item

[PDF]
[PDF]
[PDF]

This item appears in the following Collection(s)

[-] Show simple item record