Conformational studies of biologically active molecules.
Item
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Title
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Conformational studies of biologically active molecules.
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Identifier
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AAI9912604
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identifier
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9912604
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Creator
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Antohi, Octavian.
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Contributor
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Adviser: Anne-Marie Sapse
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Date
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1998
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Physical | Chemistry, Biochemistry | Biology, Molecular
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Abstract
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Computational techniques (molecular modeling and ab initio calculations) are used in conjunction with nuclear magnetic resonance spectroscopy in order to probe and determine the conformation of a family of peptides that are related to the Saccharomyces cerevisiae alpha-Factor pheromone.;The ab initio calculations provide quantitative values for the energy barriers introduced by the usage of certain side chain constraints. These quantitative results are found to correlate well with the conformational preferences of peptides that are built around cores containing such amino acids.;The strengths and weaknesses of force field molecular modeling techniques are analyzed in detail and their applicability to the design and interpretation of experimental setups is discussed.;Both the physical chemical analysis of analogs and the calculations seem to support the currently accepted model in which a turn in the 7 to 10 region of this peptide molecule is considered to play a decisive role in its pheromonal activity. Besides shedding light on the possible biologically active conformation, the analysis of cyclized analogs clarifies the effects of lactam cycle constraints which are found to be consistently independent of the size of the peptide chain but strongly dependent on the size of the lactamization ring.;The limitations of solid state nmr dipolar dephasing experiments are discussed and a first order approximation theoretical basis for the computation of natural abundance corrections is developed. New multiple spin experiments are hypothetically considered.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
