Synthesis, conformational analysis, and biological activities of cyclic enkephalins and model cyclic peptides containing thioamides as amide bond replacements
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
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
Similar Records
Crystal structure and conformation of the cyclic hexapeptide cyclo-(Gly-L-Pro-D-Ala)/sub 2/
Substance P in Solution: Trans-to-Cis Configurational Changes of Penultimate Prolines Initiate Non-enzymatic Peptide Bond Cleavages
Related Subjects
AMIDES
CHEMICAL BONDS
ENKEPHALINS
MOLECULAR STRUCTURE
PEPTIDES
CARBON 13
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
PROTONS
TRACER TECHNIQUES
AUTONOMIC NERVOUS SYSTEM AGENTS
BARYONS
CARBON ISOTOPES
DRUGS
ELEMENTARY PARTICLES
ENDORPHINS
EVEN-ODD NUCLEI
FERMIONS
HADRONS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
NEUROREGULATORS
NUCLEI
NUCLEONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
POLYPEPTIDES
PROTEINS
RESONANCE
SPECTRA
STABLE ISOTOPES
550201* - Biochemistry- Tracer Techniques