A pH-Sensitive Peptide-Containing Lasso Molecular Switch

Abstract

Abstract:The synthesis of a peptide-containing lasso molecular switch by a selfentanglement strategy is described. The interlocked [1] rotaxane molecular machine consists of a benzometaphenylene [25]crown-8 (BMP25C8) macrocycle surrounding a molecular axle. This molecular axle contains a tripeptidic sequence and two molecular stations: a N-benzyltriazolium and a pH-sensitive anilinium station. The tripeptide is located between the macrocycle and the triazolium station, so that its conformation can be tailored depending on the shuttling of the macrocycle from one station to the other. At acidic pH, the macrocycle resides around the anilinium moiety, whereas it shuttles around the triazolium station after deprotonation. This molecular machinery thus forces the lasso to adopt a tightened or a loosened conformation.

An amide hydrogen bond templated [1]rotaxane displaying a peptide motif – demonstrating an expedient route to synthetic mimics of lasso peptides

“…When compared to prior work from the laboratories of Coutrot 8 and Bode, 9 the synthetic route reported here has the potential to generate better mimics of naturally occurring lasso peptides. In the previous cases, the entangled structure arises from the non-amide templation of a protonated ammonium passing through a 24-crown-8 macrocycle.…”

“…6 Synthetic [1]rotaxanes 7 are structurally equivalent to lasso peptides, but examples that display peptide sequences are rare. 8,9 Recently we have rapidly prepared [2]rotaxanes [10][11][12] by use of hydrogen bond templation 13 and CuAAC click chemistry to stopper a simple amide half-axle component threaded through an isophthalamide macrocycle. 14 Here we are reporting an adaptation of this method to rapidly prepare a [1]rotaxane displaying a Gly-Gly-Gly-Gly peptide sequence within the key loop region, by appending and then cyclizing a peptide chain on a novel "scaffold" [2]rotaxane.…”

Gas‐phase conformations of capistruin – comparison of lasso, branched‐cyclic and linear topologies

“…The lasso topology is essential to the biological activity of these peptides, which includes enzyme inhibition, receptor antagonism, antibacterial and anti‐HIV activities. Lasso peptides exhibit resistance against heat and proteolytic degradation and cannot be produced by chemical synthesis . However, certain lasso peptides have been shown to unthread under denaturing condition .…”

Ion Transport Properties and Ionicity of 1,3-Dimethyl-1,2,3-Triazolium Salts with Fluorinated Anions

“…Imidazolium salts are the golden standard at the moment [ 2 ] but 1,2,3-triazolium salts (TRSs) are a class of ILs which receive continuously increasing interest due to their facile accessibility via Cu(I)-catalyzed Huisgen-type 1,3-dipolar cycloaddition (CuAAC, “click” reaction), and subsequent N -alkylation in quantitative yields [ 1 , 3 , 4 , 5 , 6 ]. Optionally, the anion can be exchanged in an additional so-called salt metathesis step [ 1 ], which enables different combinations of cations and anions for TRSs with tuneable properties for a plethora of applications as reaction media [ 7 , 8 ], antifungal agents [ 9 , 10 ], molecular machines [ 11 , 12 ], sensors [ 13 ], anticancer drugs [ 14 ], precursors for N -heterocyclic carbene ligands [ 15 , 16 ], or electrolyte systems in electrochemical devices such as batteries, fuel cells, transistors, and solar cells [ 17 , 18 , 19 , 20 ].…”