Heterochirality Restricts the Self-Assembly of Phenylalanine Dipeptides Capped with Highly Aromatic Groups

• Published in: The journal of physical chemistry. B Vol. 124; no. 28; pp. 5913 - 5918
• Main Authors: Gil, Ana M, Casanovas, Jordi, Mayans, Enric, Jiménez, Ana I, Puiggalí, Jordi, Alemán, Carlos
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16-07-2020
• Subjects: B: Biophysics; Physical Chemistry of Biological Systems and Biomolecules; Dipeptides; Hydrophobic and Hydrophilic Interactions; Peptides; Phenylalanine; Solvents
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/acs.jpcb.0c04513

The influence of stereochemistry on the self-assembly of phenylalanine (Phe) dipeptides bearing aromatic fluorenyl groups at both the N- and C-termini (Fmoc, OFm) has been investigated. For this purpose, Fmoc–d-Phe–l-Phe–OFm and Fmoc–l-Phe–l-Phe–OFm have been examined considering a wide variety of solvents, which differ in dielectric constant and volatility. Results reveal that replacement of l-Phe by d-Phe has a major impact on the self-assembly propensities, restricting drastically the structural diversity and polymorphism shown by the homochiral dipeptide. Thus, the analogous heterochiral dipeptide shows a great propensity to form micro/nanofibers, independently of the environmental conditions. Theoretical calculations revealed that the stability of antiparallel disposition is much higher (a factor of ca. 15) for Fmoc–d-Phe–l-Phe–OFm than that for Fmoc–l-Phe–l-Phe–OFm, which has been attributed to the hydrophobic core formed in the former. Overall, results suggest that control of the backbone chirality is a potent and versatile strategy to drive and finely tune the self-assembly propensities of highly aromatic peptides.