Bioactive conformation of linear peptides in solution: an elusive goal?
Bioactive peptides of natural origin have, in general, short linear sequences, and are characterized by a large conformational flexibility. It is very difficult to study their conformation in solution since they exist, almost invariably, as a complex mixture of numerous conformers, most of which are extended. The so-called bioactive conformation may be one of them, although the solvents used in solution studies often have properties drastically different from those of the biological system in which the peptide acts. There is, however, no simple way of identifying the bioactive conformation amid the many existing conformers. It is possible to approach a solution to this problem using two distinct strategies: (a) Limiting the conformational freedom of the peptide, e.g., by increasing the viscosity of the solution and decreasing the temperature, in the assumption that the bioactive conformation is, even slightly, more stable than the others. (b) Trying to mimic in solution the physicochemical features of the more reliable receptor models. These two approaches will be illustrated with examples taken mainly from opioid peptides.
Temussi
P A
PA
Picone
D
D
Castiglione-Morelli
M A
MA
Motta
A
A
Tancredi
T
T
D000595:Amino Acid Sequence; D004723:Endorphins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides; D011487:Protein Conformation; D011957:Receptors, Opioid / Q000378:metabolism*; D012996:Solutions; D013329:Structure-Activity Relationship
D004723:Endorphins; D010455:Peptides; D011957:Receptors, Opioid; D012996:Solutions