Effect of Stereochemistry and Hydrophobicity on the Self‐Assembly of Phe‐Phe‐Nucleoside Conjugates

Abstract: Molecular self‐assembly of the minimal diphenylalanine (Phe‐Phe) peptide building block shows unique morphological organizations and potential utility in biochemistry and biomaterials applications. Furthermore, the molecular engineering of nucleoside‐conjugated Phe‐Phe scaffolds allows the formation of diverse architectures with tunable biophysical properties. While the self‐assembly of homochiral l‐dipeptides is well characterized, stereochemistry is known to determine the conformation, which also governs self‐assembly through molecular packing effects. Here, the effect of stereochemistry and hydrophobicity on Phe‐Phe nucleoside conjugates using all four diastereomers [(l) Phe‐(l) Phe, (d) Phe‐(dPhe, (l) Phe‐(d) Phe, and (d) Phe‐(l) Phe] of Phe‐Phe conjugates is systematically studied. The homochiral peptides form well‐defined nanorods while the heterochiral dipeptides do not form any regular structures. Since heterocyclic nucleobases can self‐assemble through hydrogen‐bonded complementary base‐pairing, the self‐assembly of chiral nucleoside‐conjugated Phe‐Phe peptides is examined. All conjugated Phe‐Phe peptides form seamless spherical particles. The completely or partially deprotected peptides do not assemble to any defined nanostructures suggesting that self‐assembly is governed by the precise hydrophobic/hydrophilic balance in the assembling units. Contact angle measurements of the diastereomeric peptides reveal a subtle difference in stereochemistry‐dependent molecular hydrophobicity. Taken together, it is revealed that the combination of chirality together with hydrophobic/hydrophilic balance within the peptides dictates the self‐assembly of Phe‐Phe dipeptide nucleoside conjugates.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Effect of Stereochemistry and Hydrophobicity on the Self‐Assembly of Phe‐Phe‐Nucleoside Conjugates ; day:22 ; month:04 ; year:2022 ; extent:11 ; Macromolecular chemistry and physics ; (22.04.2022) (gesamt 11)

Contributors, Places and Time

• Creator: Tiwari, Om Shanker ; Ganesh, Krishna N. ; Gazit, Ehud

Further information

• DOI: 10.1002/macp.202200011
• URN: urn:nbn:de:101:1-2022042215323873737080
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:22 AM CEST