Sequence-Selective Decapeptide Synthesis by the Parallel Operation of Two Artificial Molecular Machines

Abstract

We report on the preparation of a decapeptide through the parallel operation of two rotaxane-based molecular machines. The synthesis proceeds in four stages: (1) simultaneous operation of two molecular peptide synthesizers in the same reaction vessel; (2) selective residue activation of short-oligomer intermediates; (3) ligation; (4) product release. Key features of the machine design include the following: (a) selective transformation of a thioproline building block to a cysteine (once it has been incorporated into a hexapeptide intermediate by one molecular machine); (b) a macrocycle-peptide hydrazine linkage (as part of the second machine) to differentiate the intermediates and enable their directional ligation; and (c) incorporation of a Glu residue in the assembly module of one machine to enable release of the final product while simultaneously removing part of the assembly machinery from the product. The two molecular machines participate in the synthesis of a product that is beyond the capability of individual small-molecule machines, in a manner reminiscent of the ligation and post-translational modification of proteins in biology.

Nano-Hybrid Au@LCCs Systems Displaying Anti-Inflammatory Activity

“…In the last decades, nanotechnological strategies combined with a supramolecular approach allowed us to reach geometrically well-defined and responsive nanodevices [ 1 , 2 ] with a relevant impact in several fields [ 3 , 4 , 5 ]. In particular, the engineering of suitable nanomaterials provides high-performance nanomedicine systems including drug/gene delivery carriers, imaging tools, tissue scaffolds, and biosensors [ 6 , 7 , 8 , 9 ].…”

Photochemical Energy Conversion with Artificial Molecular Machines

“…The key concepts, most significant achievements, and perspectives of such systems have been discussed in a few monographs 19 − 21 and edited books 22 − 24 and in several excellent reviews. 25 − 31 The high scientific value of this research, and its potential to enable revolutionary applications in several areas of technology and medicine, 32 − 38 was recognized in 2016 by the award of the Nobel in Prize in Chemistry to Jean-Pierre Sauvage, Fraser Stoddart, and Ben Feringa “for the design and synthesis of molecular machines”. 39 …”

“…More details on the mechanisms by which energy stimuli can be exploited to rectify random thermal motion—for example, how the energy released in ATP hydrolysis is converted into mechanical work in biomolecular motors—can be found elsewhere. 8 , 9 , 11 , 27 − 29 , 38 , 40 …”

“…During the past four decades, the application of an engineering mentality to research in synthetic, physical, and analytical chemistry has led to the development of a large variety of artificial molecular machines and motors, utilizing a wide range of molecular and supramolecular species, both manmade and of biological origin. The key concepts, most significant achievements, and perspectives of such systems have been discussed in a few monographs − and edited books − and in several excellent reviews. − The high scientific value of this research, and its potential to enable revolutionary applications in several areas of technology and medicine, − was recognized in 2016 by the award of the Nobel in Prize in Chemistry to Jean-Pierre Sauvage, Fraser Stoddart, and Ben Feringa “for the design and synthesis of molecular machines” …”

“…When the perturbation ends, or an opposite input is activated, the free energy profile is reset, and the object returns on the original position, again taking advantage of Brownian motion (d). More details on the mechanisms by which energy stimuli can be exploited to rectify random thermal motionfor example, how the energy released in ATP hydrolysis is converted into mechanical work in biomolecular motorscan be found elsewhere. ,,,− ,, …”