The Synthesis of D-Oxytocin, the Enantiomer of the Posterior Pituitary Hormone, Oxytocin¹

Abstract

but the exo/endo ratio is still only about 30. This low ratio stands in striking contrast to the one observed for solvolyses,8 which is ~105 at 25°, and it is concluded that neighboring group assistance is energetically less favored in the gas phase than in solution. Two reasons probably do account for this: firstly, neighboring group migration is usually associated with some loss of rotational entropy for the reactant on ring closure to the transition state.9 This entropy loss, which impedes reactivity, will inevitably be more pronounced in the gas phase than in solution. Secondly, since neighboring group assistance depends, among other factors, critically upon the charge development at the migrating center, the driving force for migration in the gas phase is reduced.

All-D-Enantiomers of β-Amyloid Exhibit Similar Biological Properties to All-L-β-Amyloids

“…This is the smallest commonly studied fragment of A␤ that retains both the ability to form ␤-sheet-containing fibrils and neurotoxicity (19). An additional advantage of A␤ [25][26][27][28][29][30][31][32][33][34][35] is that it can be modeled relatively easily, and information on the alignment of the antiparallel strands as well as the importance of various side chain interactions in formation of the A␤ fibrils and in defining the surface topography necessary for neurotoxicity can be investigated. In the antiparallel ␤-sheet conformation, the surface topography is determined by the amino acid sequence and the alignment of adjacent strands in the ␤-sheet.…”

“…Peptide Synthesis-A␤ 1-42 , A␤ 25-35 (GSNKGAIIGLM), and scrambled sequence A␤ [25][26][27][28][29][30][31][32][33][34][35] (12) were synthesized from either all-D-or all-Lamino acids using solid phase Fmoc (N-(9-fluorenyl)methoxycarbonyl) amino acid chemistry and purified by reverse phase HPLC, as described previously (9). The purified peptides were then routinely analyzed by electrospray mass spectroscopy (9).…”

“…Similar issues of ligand stereospecificity have been investigated in several recent studies by comparing the binding and or activities of D-and L-enantiomers of small peptide ligands (15,16). In the current study, we have utilized a comparable paradigm, synthesizing the all-D-and all-L-amino acid stereoisomers of the truncated biologically active A␤ [25][26][27][28][29][30][31][32][33][34][35] and the full-length A␤ 1-42 peptide, and compared their physical and biological properties to determine whether the interaction of A␤ with biologically relevant cells is stereospecific. …”

“…For example, glutamate receptors readily discriminate L-versus D-antagonistic agents (29). We have analyzed both the physical and biological properties of the all-D-enantiomers of A␤ [25][26][27][28][29][30][31][32][33][34][35] and A␤ and have compared them with their corresponding all-L-enantiomers. With the exception of the CD spectropolarimetry study, which produced mirror image spectrums, both all-D-enantiomers exhibited essentially identical physical and biological properties to their all-L-enantiomers.…”

“…To further investigate the mechanism of A␤ neurotoxicity, we synthesized the all-D-and all-Lstereoisomers of the neurotoxic truncated form of A␤ (A␤ [25][26][27][28][29][30][31][32][33][34][35] ) and the full-length peptide (A␤ 1-42 ) and compared their physical and biological properties. We report that the purified peptides exhibit nearly identical structural and assembly characteristics as assessed by high performance liquid chromatography, electron microscopy, circular dichroism, and sedimentation analysis.…”