The neuropeptide galanin is a 29- or 30-residue peptide whose physiological functions are mediated by G-protein-coupled receptors. Galanin's agonist activity has been shown to be associated with the N-terminal sequence, galanin(1-16). Conformational investigations previously carried out on full-length galanin have, furthermore, indicated the presence of a helical conformation in the neuropeptide's N-terminal domain. Several cyclic lactam analogues of galanin(1-16)-NH2 were prepared in an attempt to stabilize an N-terminal helix in the peptide. Here we describe and compare the solution conformational properties of these analogues in the presence of SDS micelles as determined by NMR, CD, and fluorescence spectroscopy. Differences in CD spectral profiles were observed among the compounds that were studied. Both c[D4, K8]Gal(1-16)-NH2 and c[D4,K8]Gal(1-12)-NH2 adopted stable helical conformations in the micelle solution. On the basis of the analyses of their respective alpha H chemical shifts and NOE patterns, this helix was localized to the first 10 residues. The distance between the aromatic rings of Trp2 and Tyr9 in c[D4, K8]Gal(1-16)-NH2 was determined to be 10.8 +/- 3 A from fluorescence resonance energy transfer measurements. This interchromophore spacing was found to be more consistent with a helical structure than an extended one. Removal of the Gly1 residue in compounds c[D4,K8]Gal(1-16)-NH2 and c[D4, K8]Gal(1-12)-NH2 resulted in a loss of helical conformation and a concomitant reduction in binding potency at the GalR1 receptor but not at the GalR2 receptor. The nuclear Overhauser enhancements obtained for the Gly1 deficient analogues did, however, reveal the presence of nascent helical structures within the N-terminal sequence. Decreasing the ring structure size in c[D4, K8]Gal(1-16)-NH2 by replacing Lys8 with an ornithine residue or by changing the position of the single lysine residue from eight to seven was accompanied by a complete loss of helical structure and dramatically reduced receptor affinity. It is concluded from the data obtained for the series of cyclic galanin(1-16)-NH2 analogues that both the ring structure size and the presence of an N-terminal glycine residue are important for stabilizing an N-terminal helix in these compounds. However, although an N-terminal helix constitutes a predominant portion of the conformational ensemble for compounds c[D4,K8]Gal(1-16)-NH2 and c[D4, K8]Gal(1-12)-NH2, these peptides nevertheless are able to adopt other conformations in solution. Consequently, the correlation between the ability of the cyclic galanin analogues to adopt an N-terminal helix and bind to the GalR1 receptor may be considered as a working hypothesis.

The detonation energies of several high explosives are evaluated from the results of chemical-equilibrium computer code named EXPLO5. Two methods of the evaluation of detonation energy are applied: (a) direct evaluation from the internal energy of detonation products at the CJ point and the energy of shock compression of the detonation products, i.e. by equated the detonation energy and the heat of detonation, and (b) evaluation from the expansion isentrope of detonation products, applying the JWL model. These energies are compared to the energies computed from cylinder test derived JWL coefficients. It is found out that the detonation energies obtained directly from the energy of detonation products at the CJ point are uniformly to high (0.9445?0.577 kJ/cm3), while the detonation energies evaluated from the expansion isentrope, are in a considerable agreement (0.2072?0.396 kJ/cm3) with the energies calculated from cylinder test derived JWL coefficients

A generalization of the Dirac field equation in three-dimensional Minkowski space-time to the case of the $\bar{SL}(3,R)$ $\subset$ $\bar{SA}(3,R)$ symmetry is considered. Constraints that ensure a correct physical interpretation of the corresponding particle states are presented. Dirac-like equations based on both multiplicity-free and generic infinite-component $\bar{SL}(3,R)$ representations are outlined.