Diverging conformations guide dipeptide self-assembly into crystals or hydrogels

Abstract

The prediction of dipeptide assembly into crystals or gels is challenging. This work reveals the diverging conformational landscape that guides self-organization towards different outcomes. In silico and experimental data enabled...

Supramolecular Hydrogels and Water Channels of Differing Diameters from Dipeptide Isomers

“…This observation was in agreement with the marked tendency of the fibrils of d -Phe- l -Nle ( 4 ) to mutually interact as they are oriented parallel to each other, as seen by TEM (Figure D). The marked tendency to crystallize of d -Phe- l -Nle ( 4 ) was found for other heterochiral dipeptides with N-terminal Phe and a C-terminal aliphatic amino acid, such as Leu, and was recently ascribed to the presence of conformers in solution with folded side chains similarly to those found in the corresponding crystal structures . The metastable character of fibrils that over time covert into microcrystals is not new …”

“…The second observation can be related to the fact that hydrophobic and heterochiral dipeptides with Phe at the N-terminus and an aliphatic amino acid at the C-terminus were found to adopt conformers with both folded and extended side chains, resulting in metastable gels, whereby initially the dipeptides adopt gelling extended conformers, and later, they crystallize through the self-assembly of folded conformers . Instead, more stable gels can arise from heterochiral dipeptides with an aliphatic amino acid at the N-terminus and Phe at the C-terminus, because they tend to adopt gelling extended conformers . Besides, presence of the linear Nle side chain, as opposed to the branched Leu regioisomer, favored self-assembly, and reduced the mgc .…”

“…The first observation can be explained by noting that heterochirality was found to increase the dipeptide hydrophobicity, and self-assembly in water is driven by the hydrophobic collapse. The second observation can be related to the fact that hydrophobic and heterochiral dipeptides with Phe at the N-terminus and an aliphatic amino acid at the C-terminus were found to adopt conformers with both folded and extended side chains, resulting in metastable gels, whereby initially the dipeptides adopt gelling extended conformers, and later, they crystallize through the self-assembly of folded conformers . Instead, more stable gels can arise from heterochiral dipeptides with an aliphatic amino acid at the N-terminus and Phe at the C-terminus, because they tend to adopt gelling extended conformers .…”

“…The marked tendency to crystallize of D-Phe-L-Nle (4) was found for other heterochiral dipeptides with N-terminal Phe and a C-terminal aliphatic amino acid, such as Leu, 31 and was recently ascribed to the presence of conformers in solution with folded side chains similarly to those found in the corresponding crystal structures. 32 The metastable character of fibrils that over time covert into microcrystals is not new. 34 Visible and UV Resonance Raman (UVRR) Spectroscopies.…”

“…32 Instead, more stable gels can arise from heterochiral dipeptides with an aliphatic amino acid at the Nterminus and Phe at the C-terminus, because they tend to adopt gelling extended conformers. 32 Besides, presence of the linear Nle side chain, as opposed to the branched Leu regioisomer, favored self-assembly, and reduced the mgc. 31 We inferred that the higher conformational flexibility of Nle side chain favored supramolecular packing, as noted for similar tripeptides.…”