Conformational analysis of neuropeptide Y-[18–36] analogs in hydrophobic environments

• Published in: Biophysical journal Vol. 72; no. 1; pp. 238 - 246
• Main Authors: Lazoura, E., Maidonis, I., Bayer, E., Hearn, M.T., Aguilar, M.I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 1997
• Subjects: Amino Acid Sequence; Angiotensin I - chemistry; Angiotensin II - chemistry; Angiotensin III - chemistry; Chromatography, High Pressure Liquid; Circular Dichroism; Models, Structural; Molecular Sequence Data; Neuropeptide Y - chemistry; Peptide Fragments - chemistry; Peptides - chemistry; Protein Conformation; Protein Structure, Secondary; Structure-Activity Relationship; Thermodynamics
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/S0006-3495(97)78662-4

The interactive and conformational behavior of a series of neuropeptide Y-[18–36] (NPY-[18–36]) analogs in hydrophobic environments have been investigated using reversed-phase high-performance liquid chromatography (RP-HPLC) and circular dichroism (CD) spectroscopy. The peptides studied comprised a series of 16 analogs of NPY-[18–36], each containing 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 spectroscopy. Retention parameters related to the hydrophobic contact area and the affinity of interaction were determined with an n-octadecyl (C18) adsorbent. Structural transitions for all peptides were manifested 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 for maintenance of the alpha-helical conformation. Moreover, L-->D amino acid residue substitutions within the N- and C-terminal regions, as well as Asn29 and Leu30, do not appear to affect the secondary structure of the peptide. These studies demonstrate that RP-HPLC provides a powerful adjunct for investigations into the induction of stabilized secondary structure in peptides upon their interaction with hydrophobic surfaces.