Quantifying End‐to‐End Conformational Communication of Chirality through an Achiral Peptide Chain

Abstract

Successful communication: Two diastereotopic protons more than 60 bonds from the nearest chiral center appear as an AB system, showing that the intervening structure is a well‐ordered helix. Decay of anisochronicity quantifies the linear persistence of a helix of achiral amino acids: as little as 3.5 % of the chiral influence is lost with each additional achiral residue.

Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor

“…19 In solution, these "foldamers" 20 populate almost exclusively 21 two rapidly exchanging conformational states of left or right handed helical screw sense, with the relative population of these two states being remarkably sensitive to chiral influences. [22][23][24][25] A chiral ligand covalently 15 or non-covalently 16 bound to one terminus of an Aib foldamer will propagate its conformational influence through the entire foldamer length. 26 In this way endto-end transmission of binding information over multi-nanometre distances has been accomplished through Aib foldamers dissolved in organic solvents.…”

End-to-end conformational communication through a synthetic purinergic receptor by ligand-induced helicity switching

“…The strong tendency of the foldamer (an oligomer of 2-aminoisobutyric acid, or Aib) to maintain a 3 10 helical conformation 18,32,33 means that this perturbation propagates along the entire length of the oligomer, and is detectable spectroscopically at some distance from the binding site. In the system we present here, NMR is used to report the resulting unequal populations of M and P helices.…”

“…Given that the fidelity of information encoded in the screw-sense preference of helical oligomers of Aib decays only slowly as the length of the helix increases 18,35 , we reasoned that it should be possible for our ligand-switchable receptor structures to communicate information over distances commensurate with, for example, the thickness of a phospholipid bilayer ( 2-4 nm) 46 . We therefore synthesized receptor 5 (Fig.…”

“…It is well established that a single chiral residue sited at the terminus of an otherwise achiral helical oligomer is sufficient to bias the screw-sense of the oligomer [18][19][20][21][22] , and remote spectroscopic reporters have been used to detect the resulting conformational preference 9,[21][22][23][24][25][26][27] . Helical oligomers may consequently behave as communication devices, because the relayed conformational change allows stereochemistry at one end of the oligomer to influence a reporter several nanometres away 28 .…”

Remote Control of the Planar Chirality in Peptide‐Bound Metallomacrocycles and Dynamic‐to‐Static Planar Chirality Control Triggered by Solvent‐Induced 310‐to‐α‐Helix Transitions

“…First, ar ight-handed (P)-3 10 -helix is induced in the dynamic helical oligopeptides by ac hiral amino acid residue far from the macrocyclic framework. The induced planar chirality remains dynamic in chloroform and acetonitrile,but is almost completely locked in fluoroalcohols as ar esult of the solventinduced transition of the peptide chains from a3 10 -helix to aw ider a-helix, which freezes the rotation of the pendant peptide units around the macrocycle.Long-range communication is ubiquitous in biological systems,f or example in allosteric enzymes.[1] Such longrange information transfer has been successfully achieved in artificial helical systems based on the chiral domino effect, [2] through which an excess of either ar ight-(P)o rl eft-handed (M)h elical conformation can be induced in dynamic helical polymers and oligomers including peptides that are composed of achiral components by covalently or noncovalently introducing chiral residues at the chain ends.T aking advantage of this unique chiral domino effect, we recently succeeded in the multistep remote control of the dynamic metal-centered chirality (D or L)ofcomplexes coordinated by 2,2'-bipyridine (bpy) ligands bearing dynamic helical oligopeptides.[3] We anticipated that this multistep remote-control strategy based on the chiral domino effect would be applicable to control other types of complex supramolecular chirality, [4] such as the planar chirality of macrocycles. [5] To this end, we synthesized novel dynamic peptide-bound Ni II -salphen-based macrocycles [6] (Figure 1a)i nw hich the planar chirality results from the relative orientations of the peptide-bound phenylene units,w hich can rotate around the macrocyclic plane via the peptide chains passing through the inside of the macrocyclic cavity,t hus producing four interconvertible diastereomers [(pS,pS,pS), (pR,pS,pS), (pR,pR,pS), and (pR,pR,pR)].…”