Structural transitions involved in a novel amyloid‐like β‐sheet assemblage of tripeptide derivatives

Self‐assembly of two tripeptide derivatives containing three nonpolar isoleucine moieties and polar oxyethylene groups are studied in methanol. Peptide A [CH 3 (OCH 2 CH 2 ) 3 OCH 2 CO(Ile) 3 OCH 3 ] and peptide B [CH 3 (OCH 2 CH 2 ) 3 OCH 2 CO(Ile) 3 NH (CH 2 CH 2 O) 3 CH 3 ] take a mixture of unordered and helical conformation at low concentration (8.5×10 −4 M ). However, at high concentration (2×10 −3 M ), both the peptide showed significant increase in the helical conformation. An interesting conformational transition of peptides A and B at various methanol contents was observed in the solvated films of these compounds by spectroscopic methods like the far‐uv circular dichroism and Fourier transform infrared (FT‐IR) techniques. Peptide B , which contains more polar oxyethylene groups than A , showed a highly cooperative conformational transition when the methanol content was decreased. This transition was characterized by a large increase of β‐sheet, retaining a α‐helical contribution. Peptide A showed a conformational transition resulting in a β‐sheet in the aggregated state. From the CD spectra, the ratio in the ellipticity indicates that peptide B forms twisted antiparallel β‐sheet conformation, whereas peptide A takes a parallel β‐sheet conformation. The results obtained in this work indicates the role of polar derivatization on the conformational preference of peptides having similar sequence. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 336–345, 2003