Thermally induced cyclization of _L‐isoleucyl‐_L‐alanine in solid state: Effect of dipeptide structure on reaction temperature and self‐assembly

Abstract

Thermal treatment of short-chain oligopeptides is able to initiate the process of their self-assembly with the formation of organic nanostructures with unique properties. On the other hand, heating can lead to a chemical reaction with the formation of new substances with specific properties and ability to form structures with different morphology. Therefore, in order to have a desired process, researcher needs to find its temperature range. In the present work, cyclization of L -isoleucyl-Lalanine dipeptide in the solid state upon heating was studied. Kinetic parameters of this reaction were estimated within the approaches of the nonisothermal kinetics.The correlation between side chain structure of dipeptides and temperature of their cyclization in the solid state was found for the first time. This correlation may be used to predict the temperature, at which dipeptide self-assembly changes to chemical reaction. The differences in self-assembly of linear and cyclic dipeptides were demonstrated using atomic force microscopy. The effect of dipeptide concentration in a source solution and an organic solvent used on self-assembly of dipeptides was shown. The new information obtained on the thermal properties and self-assembly of linear and cyclic forms of L -isoleucyl-L -alanine may be useful for the design of new nanomaterials based on oligopeptides, as well as for the synthesis of cyclic oligopeptides.

Diketopiperazine Gels: New Horizons from the Self-Assembly of Cyclic Dipeptides

“…The appropriate reaction temperature depends on the nature of the peptide sequence. For example, Gly-Gly needs 230 °C, while Phe-Phe 147 °C [ 90 ] or 125 °C [ 91 ], suggesting a correlation between the reaction minimum temperature and the amino acid side-chain steric hindrance. Cyclization indeed requires molecular mobility, which is governed by the nature of the side chains in the solid state.…”

“…The melting points of Gly-Gly and Phe-Phe are respectively 262–264 °C and 288–290 °C, thus confirming that the reaction occurred in a solid state and probably above the glass transition temperature ( T g ). The latter depends on the sample preparation when manufactured; from that point onwards, CDP molecules do not maintain random conformations and, instead, they start to reorganize in the solid structure, since rotations and translations are possible [ 90 ].…”

Cyclic dipeptides: Biological activities and self‐assembled materials

“…[13] Besides, the environmental conditions played a significant role in the dynamic process of CDP self-assembly. [65][66] As a result of multiple interactions, CDPs self-assembled into various ordered nanostructures and functional architectures.…”

“…When the solvent was changed from HFIP to methanol, selfassembling cyclo(L-Ile-L-Ala) exhibited fibrous structures. [66] Considering the above factors, we can modulate CDPs flexibly via selecting the type of amino acids, modifying the side chain, and changing self-assembly conditions to obtain desired nanostructures.…”

“…When the solvent was changed from HFIP to methanol, self‐assembling cyclo(L‐Ile‐L‐Ala) exhibited fibrous structures. [ 66 ]…”