Self-Assembly of Tetraphenylalanine Peptides

• Published in: Chemistry : a European journal Vol. 21; no. 47; pp. 16895 - 16905
• Main Authors: Mayans , Enric, Ballano, Gema, Casanovas, Jordi, Díaz , Angélica, Pérez-Madrigal , Maria M., Estrany, Francesc, Puiggalí , Jordi, Cativiela, Carlos, Alemán , Carlos
• Format: Journal Article Publication
• Language: English
• Published: Weinheim WILEY-VCH Verlag 16-11-2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Assembly; beta sheet; Chemistry; Enginyeria química; Esters; Fluorenes - chemistry; hydrogen bonds; Mathematical models; Molecular Dynamics Simulation; Nanostructure; Nanotubes; Nanotubes - chemistry; Peptides; Peptides - chemical synthesis; Peptides - chemistry; phenylalanine; Phenylalanine - analogs & derivatives; Phenylalanine - chemical synthesis; Phenylalanine - chemistry; pi interactions; Pèptids; Self assembly; Àrees temàtiques de la UPC; nanotubes; phenylalanine; beta sheet; hydrogen bonds; pi interactions
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.201501793

Three different tetraphenylalanine (FFFF) based peptides that differ at the N‐ and C‐termini have been synthesized by using standard procedures to study their ability to form different nanoassemblies under a variety of conditions. The FFFF peptide assembles into nanotubes that show more structural imperfections at the surface than those formed by the diphenylalanine (FF) peptide under the same conditions. Periodic DFT calculations (M06L functional) were used to propose a model that consists of three FFFF molecules defining a ring through head‐to‐tail NH3+⋅⋅⋅−OOC interactions, which in turn stack to produce deformed channels with internal diameters between 12 and 16 Å. Depending on the experimental conditions used for the peptide incubation, N‐fluorenylmethoxycarbonyl (Fmoc) protected FFFF self‐assembles into a variety of polymorphs: ultra‐thin nanoplates, fibrils, and star‐like submicrometric aggregates. DFT calculations indicate that Fmoc‐FFFF prefers a parallel rather than an antiparallel β‐sheet assembly. Finally, coexisting multiple assemblies (up to three) were observed for Fmoc‐FFFF‐OBzl (OBzl = benzyl ester), which incorporates aromatic protecting groups at the two peptide terminals. This unusual and noticeable feature is attributed to the fact that the assemblies obtained by combining the Fmoc and OBzl groups contained in the peptide are isoenergetic.
Variety show! Three different tetraphenylalanine‐based peptides that differ at the N‐ and C‐termini have been synthesized by using standard procedures to study their ability to form different nanoassemblies (e.g., nanotubes, see figure) under a variety of conditions.