Synthesis, conformational analysis, and biological activities of cyclic enkephalins and model cyclic peptides containing thioamides as amide bond replacements
Thesis/Dissertation
·
OSTI ID:6948542
This thesis describes the first applications of the thioamide surrogate ({psi}(CSNH)) in model cyclic peptides and cyclic enkephalins. The solution phase synthesis and conformational analysis of two model cyclic endothiopentapeptides, cyclo(D-Phe-Pro{psi} (CSNH)Gly-Pro-Gly) (I) and cyclo(D-Phe-Pro-Gly-Pro{psi}(CSNH)Gly) (II), are reported. The conformations of I and II were analyzed using several 1 and 2D NMR techniques, such as INDOR, temperature and concentration dependence, {sup 1}H-{sup 1}H and {sup 1}H-{sup 13}C COSY, ROESY, and magnetization transfer. Compound I displayed the same general conformation as its parent in CDCl{sub 3}, but the {gamma}-turn hydrogen bond appeared to be weaker, while the {beta}-turn hydrogen bond appeared to be stronger. In DMSO-d{sub 6}, this molecule existed in two conformations in a ratio of 2:1. The major conformer appeared to be the same as that in CDCl{sub 3}, while the second contained at least one cis X-Pro bond, most likely at the Gly{sup 1}-Pro{sup 2} position. Compound II displayed the same conformation as its parent in both solvents. The {gamma}-turn hydrogen bond again appeared to be weaker in CDCl{sub 3}, but comparable with the parent in DMSO-d{sub 6}. Molecular modeling studies of I and II indicated the Pro {psi} angle increased by {approx}6{degree} when a thiocarbonyl was present, thereby reducing steric interactions with the Pro {beta} methylene.
- Research Organization:
- Louisville Univ., KY (USA)
- OSTI ID:
- 6948542
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMIDES
AUTONOMIC NERVOUS SYSTEM AGENTS
BARYONS
CARBON 13
CARBON ISOTOPES
CHEMICAL BONDS
DRUGS
ELEMENTARY PARTICLES
ENDORPHINS
ENKEPHALINS
EVEN-ODD NUCLEI
FERMIONS
HADRONS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
MOLECULAR STRUCTURE
NEUROREGULATORS
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
NUCLEI
NUCLEONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
PROTONS
RESONANCE
SPECTRA
STABLE ISOTOPES
TRACER TECHNIQUES
59 BASIC BIOLOGICAL SCIENCES
AMIDES
AUTONOMIC NERVOUS SYSTEM AGENTS
BARYONS
CARBON 13
CARBON ISOTOPES
CHEMICAL BONDS
DRUGS
ELEMENTARY PARTICLES
ENDORPHINS
ENKEPHALINS
EVEN-ODD NUCLEI
FERMIONS
HADRONS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
MOLECULAR STRUCTURE
NEUROREGULATORS
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
NUCLEI
NUCLEONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
PROTONS
RESONANCE
SPECTRA
STABLE ISOTOPES
TRACER TECHNIQUES