SummaryThe Schiff base of all-trans-retinal was investigated in organic solution by 'H-and 13C-NMR. at high field. Complete assignment of the 'H-NMR. peaks of N-butyl-(all-trans-retiny1idene)amine (2) and the N-butyl-(all-trans-retiny1idene)-ammonium ion (3) was achieved by INDOR (internuclear double resonance). The vicinal proton coupling constants of the polyene chain show that the n-bond orders remain unchanged in N-butyl-(all-trans-retiny1idene)amine relative to all-transretinal (l), but change towards larger n-delocalization in the N-butyl-(all-transretiny1idene)ammonium ion. At -6 1 a only one isomer of N-butyl-(all-trans-retinylidene)ammonium was observed. This was shown to be trans at the imine linkage and independent of the solvent. The trifluoroacetic acid counter-ion can approach the positive charge of the N-atom in the weakly polar solvent dichloromethane but not in the leveling solvent methanol. In dichloromethane the nature of the 1:l complex is a H-bonded (0-... H-Nf) ion-pair whose rate of breaking and forming is rapid at RT. Strong stabilization of the ion-pair resulted from homoconjugation with a second molecule of trifluoroacetic acid. Excess of acid efficiently diminished the isomerization rate at the C, N-bond.Introduction. -The visual response in vertebrates is initiated by the transisomerization of the pigment 1 1-cis-retinal triggering a series of conformational changes in the apoprotein opsin [l] [2]. In conjunction with an investigation of the conformation of rhodopsin in detergent micelles we have recently performed a NMR. study of the conformation and dynamics of all-trans-retinal in organic solution and after incorporation into aqueous dodecyldimethylamine oxide micelles [3]. The ordered structure of the amphiphatic detergent or lipid molecules may better simulate the actual environment of the retinal chromophore [4]. Since the linkage to the retinal in rhodopsin is generally agreed to be via the primary amino group of a lysine [5] [6] we have also included in our NMR. studies the Schiff s base of all-trans-retinal.
We report progress in elucidating the structure of nisin, a naturally occurring peptide antibiotic. Nisin contains five rings constrained by lanthionine or methyllanthionine bridges, as well as alpha, beta-unsaturated amino acids. We have determined conformations for two model compounds of ring A and a derivative of ring B through interactive nmr and computer simulation studies. High-resolution nmr techniques provides structural information, which was further refined through molecular dynamics simulations. These methods are being applied to the remaining constrained fragments of the molecule. This conformational information will be employed in an aufbau approach to determining the structure of the entire molecule.
As a continuation of o u r program t o study the structure-function relationship of the peptide hormone somatostatin, we report the synthesis and biological potencies of a series of cyclic hexapeptide analogs related to somatostatin. The parent peptide of this series was designed by Veber and coworkers, c[-Pro6-Phe'-D-Trp* -Lys9 -Thr" -Phe'l-], and has been reported t o be superactive in the inhibition of the release of growth hormone. (The superscript numbers refer to the positions of residues in native somatostatin.) The series of analogs has been designed t o examine the role of the so-called bridging region, Phe" -Proh, which has been postulated to be important in maintaining the proper conformation of the biologically active tetrapeptide, Phe-D-Trp-Lys-Thr. W e have incorporated peptidomimetics and the retro-inverso modification into the bridging region of the molecule, with the aim of affecting the conformational preferences found in the parent peptide. Results from the biological assayin vitro inhibition of growth hormoneand the conformational analysis (adjoining paper) of our analogs will provide insight into the relationship between structure and biological activity of somatostatin.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.