Spontaneous Aminolytic Cyclization and Self‐Assembly of Dipeptide Methyl Esters in Water

Abstract

Dipeptides are known to spontaneously cyclize to diketopiperazines, and in some cases these cyclic dipeptides have been shown to self‐assemble to form supramolecular nanostructures. Herein, we demonstrate the in situ cyclization of dipeptide methyl esters in aqueous buffer by intramolecular aminolysis, leading to the formation of diverse supramolecular nanostructures. The chemical nature of the amino acid side chains dictates the supramolecular arrangement and resulting nanoscale architectures. For c[LF], supramolecular gels are formed, and the concentration of starting materials influences the mechanical properties of these hydrogels. Moreover, by adding metalloporphyrins to the starting dipeptide starting solution, these become incorporated through cooperative assembly, resulting in the formation of nanofibers able to catalyse the oxidation of organic phenol in water. The approach taken here, which combines chemically activated assembly with the versatility of short peptides, demonstrates a new and easy method to achieving spontaneous formation of a variety of functional supramolecular materials using simple building blocks.

Peptide-Based Supramolecular Systems Chemistry

“…Recently, the spontaneous cyclization and self-assembly of dipeptide methyl esters was reported, where the intramolecular aminolysis leads to the formation of cyclic self-assembled structures in aqueous media. 168 The obtained morphologies were found to be sequence-specific, e.g., the dipeptide LF-OMe yields c(LF) fibers that result in gelation, whereas the sequence LL-OMe assembles into tapes and the dipeptide DF-OMe forms spherical aggregates. It was found that cooperative assembly of c(LF) and the metalloporphyrin Fe III -TMPyP produced nanofibers that catalyze the oxidation of organic phenol in water.…”

“…Scale bars, 500 nm; z -scales for the AFM images, −18.9 to 23.6 nm and −50 to 50 nm, respectively. (A,B) Reproduced with permission from ref . Copyright 2020 Springer Nature.…”

“…Supramolecular self-assembly can also provide with structural order that may be exploited to induce enhanced catalytic prowess to external chromophores. Recently, the spontaneous cyclization and self-assembly of dipeptide methyl esters was reported, where the intramolecular aminolysis leads to the formation of cyclic self-assembled structures in aqueous media . The obtained morphologies were found to be sequence-specific, e.g., the dipeptide LF-OMe yields c (LF) fibers that result in gelation, whereas the sequence LL-OMe assembles into tapes and the dipeptide DF-OMe forms spherical aggregates.…”

Supramolecular hydrogels from unprotected dipeptides: a comparative study on stereoisomers and structural isomers

“…Short peptides and their analogues have been attracting great interest in recent years as building blocks for soft matter. [1][2][3][4][5][6][7] They offer several advantages over other molecular classes, such as ease of preparation and scale-up, low cost, inherent biocompatibility and biodegradability, as well as the possibility to encode biological messages. 8 In particular, it has been shown that a sequence as short as a tripeptide possesses, on average, the ideal number of non-carbon atoms required to maximise ligand-receptor interactions to develop drug-like molecules.…”

An economical approach for peptide synthesisviaregioselective C–N bond cleavage of lactams

“…(5) The present synthetic approach is not only the first example of a metal-free C–N bond cleavage reaction for intermolecular peptide bond formation but also the most economical convergent peptide synthesis. (6) DKPs can be easily prepared according to known methods 16 b ,31 and are recognised to have unique bioactivities. 32 In addition, they are also attracting attention as new functional ingredients in foods and beverages.…”