Progress toward a novel ortho-functionalized cyclic phenylalanine dipeptide

dc.creatorNeff, Bartholomew Wayne
dc.date.available2011-02-19T00:07:33Z
dc.date.issued1997-12
dc.degree.departmentChemistryen_US
dc.description.abstractSubstance P, a neuropeptide found in various mammalian tissues, is involved a variety of physiological processes including the regulation of blood pressure, smooth muscle contraction, and cell growth. Assays have shown that the phenylalanine residues (Phe7 and Phe8) of Substance P are particularly important for receptor binding. Modeling studies, based on NMR data and P-methyl substitiution, seem to indicate a preferred conformation for the phenyl sidechains. This preferred conformation for these sidechains can be approximated, without backbone distortion, through the use of a sidechain ortho 0-CH2-O-CH2-CH2-O-CH2-0 linkage between the two residues. We report progress toward the synthesis of an ortho-linked, cyclic phenylalanine dipeptide [cyclo(Boc-Phe-Phe-O-t-Bu)] for incorporation into a Substance P analog as described above. We also report the development of a synthetic method, based on the camphorsultam-derived synthesis of phenylalanine, for the formation phenylalanines containing novel sidechain functionality. These ortho-functionalized phenylalanines are then modified with the appropriate protecting groups, coupled to form the acyclic dipeptide, and cyclized via a crown ether-like SN2 coupling with ethylene glycol.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/2346/21098en_US
dc.language.isoeng
dc.publisherTexas Tech Universityen_US
dc.rights.availabilityUnrestricted.
dc.subjectPhenyl compoundsen_US
dc.subjectSubstance Pen_US
dc.subjectPhenylalanineen_US
dc.subjectPeptidesen_US
dc.subjectMolecular dynamicsen_US
dc.titleProgress toward a novel ortho-functionalized cyclic phenylalanine dipeptide
dc.typeDissertation
thesis.degree.departmentChemistry
thesis.degree.departmentChemistry and Biochemistry
thesis.degree.disciplineChemistry
thesis.degree.grantorTexas Tech University
thesis.degree.levelDoctoral
thesis.degree.namePh.D.

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