SOLVENT STABILIZED SOLUTION STRUCTURES OF GALANIN AND GALANIN ANALOGS, STUDIED BY CIRCULAR-DICHROISM SPECTROSCOPY

Circular dichroism spectroscopy has been used to study how different s olvents stabilize secondary structure in the neuropeptide galanin (rat ), two N-terminal fragments of galanin, galanin(1-12) and galanin(1-16 ), and six other differently charged analogs. Among these analogs, the peptide M40, galanin(1-13)-Pro-Pro-Ala-Leu-Ala-Leu-Ala amide, is a hi gh affinity, receptor subtype specific galanin receptor antagonist. Th e different solvents include sodium dodecyl sulfate (SDS) micelle solu tions, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoy l-sn-glycero-3-phosphoglycerol (DOPG) vesicle solutions, 100% 1,1,1,3, 3,3-hexafluoro-2-propanol (HFP) and 100% 2,2,2-trifluoroethanol (TFE). DOPC vesicles did not change the structure of the peptides as compare d to aqueous solvent. The negatively charged DOPG vesicles and SDS mic elles induced similar changes towards alpha-helical structures in all peptides. The HFP and TFE solvents have an even stronger tendency to s tabilize alpha-helical conformations in these peptides. Since DOPG ves icles can be considered as a model system for negatively charged biolo gical membranes, the solution structures observed in the presence of D OPG or SDS may be the most relevant for the in vivo situation. Correla tions between the binding affinity of the peptides to hippocampal gala nin receptors and their observed structures in the DOPG solvent were i nvestigated.