Solvent stabilized solution structures of galanin and galanin analogs, studied by circular dichroism spectroscopy.
Circular dichroism spectroscopy has been used to study how different solvents 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 high affinity, receptor subtype specific galanin receptor antagonist. The different solvents include sodium dodecyl sulfate (SDS) micelle solutions, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-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 compared to aqueous solvent. The negatively charged DOPG vesicles and SDS micelles induced similar changes towards alpha-helical structures in all peptides. The HFP and TFE solvents have an even stronger tendency to stabilize alpha-helical conformations in these peptides. Since DOPG vesicles can be considered as a model system for negatively charged biological membranes, the solution structures observed in the presence of DOPG or SDS may be the most relevant for the in vivo situation. Correlations between the binding affinity of the peptides to hippocampal galanin receptors and their observed structures in the DOPG solvent were investigated.
Ohman
A
A
Department of Biophysics, Arrhenius Laboratories, Stockholm University, Sweden.
Lycksell
P O
PO
Andell
S
S
Langel
U
U
Bartfai
T
T
Gräslund
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002942:Circular Dichroism; D019004:Galanin; D006624:Hippocampus / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009479:Neuropeptides / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D051381:Rats; D012996:Solutions
D009479:Neuropeptides; D010455:Peptides; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D012996:Solutions; C051388:1,2-dioleoyl-sn-glycero-3-phosphoglycerol; D019004:Galanin; C017251:1,2-oleoylphosphatidylcholine