CONFORMATIONAL-ANALYSIS OF NEUROPEPTIDE Y-[18-36] ANALOGS IN HYDROPHOBIC ENVIRONMENTS

The interactive and conformational behavior of a series of neuropeptid e Y-[18-36] (NPY-[18-36]) analogs in hydrophobic environments have bee n investigated using reversed-phase high-performance liquid chromatogr aphy (RP-HPLC) and circular dichroism (CD) spectroscopy. The peptides studied comprised a series of 16 analogs of NPY-[18-36], each containi ng a single D-amino acid substitution. The influence of these single L -->D substitutions on the alpha-helical conformation of the NPY-[18-36 ] analogs in different solvent environments was determined by CD spect roscopy. Retention parameters related to the hydrophobic contact area and the affinity of interaction were determined with an n-octadecyl (C -18) adsorbent. Structural transitions for all peptides were manifeste d as significant changes in the hydrophobic binding domain and surface affinity between 4 degrees C and 37 degrees C. The results indicated that the central region of NPY-[18-36] (residues 23-33) is important f or maintenance of the alpha-helical conformation. Moreover, L-->D amin o acid residue substitutions within the N- and C-terminal regions, as well as Asn(29) and Leu(30), do not appear to affect the secondary str ucture of the peptide, These studies demonstrate that RP-HPLC provides a powerful adjunct for investigations into the induction of stabilize d secondary structure in peptides upon their interaction with hydropho bic surfaces.