1,720,982 research outputs found
Acid-mediated topological control in a functionalized foldamer
No full textInduced conformational change provides a powerful mechanism to modulate the structure and function of molecules. Here we describe the synthesis of chiral, surface-functionalized oligomeric pyridine/imidazolidin-2-one foldamers, and interrogate their acid-mediated transition between linear and helical topologies
Ion-mediated conformational switches
No full textMolecular switches are ubiquitous in Nature and provide the basis of many forms of transport and signalling. Single synthetic molecules that change conformation, and thus function, reversibly in a stimulus-dependent manner are of great interest not only to chemists but society in general; myriad applications exist in storage, display, sensing and medicine. Here we describe recent developments in the area of ion-mediated switching
Hybrid diphenylalkyne-dipeptide oligomers induce multistrand B-sheet formation
No full textFunctionalized diphenylalkynes provide a template for the presentation of protein-like surfaces composed of multistrand ?-sheets. The conformational properties of three-, four-, and seven-stranded systems have been investigated in the solid- and solution-state. This class of molecule may be suitable for the mediation of therapeutically relevant protein–protein interactions
Remote conformational control of a molecular switch via methylation and deprotonation
No full textExacting control over conformation in response to an external stimulus is the central focus of molecular switching. Here we describe the synthesis of a series of diphenylacetylene-based molecular switches, and examine their response to covalent modification and deprotonation at remote phenolic positions. A complex interplay between multiple intramolecular hydrogen bond donors and acceptors determines the global conformation
B-strand mimetic foldamers rigidified through dipolar repulsion
No full textMany therapeutically relevant protein–protein interactions contain hot-spot regions on secondary structural elements, which contribute disproportionately to binding enthalpy. Mimicry of such ?-helical regions has met with considerable success, however the analogous approach for the ?-strand has received less attention. Presented herein is a foldamer for strand mimicry in which dipolar repulsion is a central determinant of conformation. Computation as well as solution- and solid-phase data are consistent with an ensemble weighted almost exclusively in favor of the desired conformation
Cover picture: a modular synthesis of conformationally preorganised extended B-strand peptidomimetics (Chem. Eur.J. 42/2015)
No full textA Lewis acid-mediated conformational switch.
No full textMolecules that change conformation in response to a stimulus have numerous uses, such as artificial chemoreceptors, novel drug delivery strategies and liquid crystal technology. Here we describe the design, synthesis and conformational behaviour of an isonicotinamide-substituted diphenylacetylene upon recognition of Lewis acids, including metalloporphyrins. Binding of these at a remote site - the pyridyl nitrogen - increases hydrogen-bond donor ability of the proximal amide NH, causing an increased preference for the alkyne rotamer in which this hydrogen bond is maintained
Amphiphilic oligoamide a-helix peptidomimetics inhibit islet amyloid polypeptide aggregation
No full textThe abnormal deposition of proteins as insoluble plaques is associated with many diseases, including Alzheimer’s, Parkinson’s and type II diabetes. There is an unmet need for synthetic agents that are able to mediate particular steps in the pathway between soluble proteins in their native unfolded state and their insoluble ?-sheet rich aggregates. We have previously reported classes of ?-helix mimetic that agonize or antagonize islet amyloid polypeptide aggregation, depending on the presence of a lipid bilayer. Here we investigate a novel mixed benzamide and pyridylamide scaffold that gives improved activity and explores the role of side-chain polarity, backbone rigidity and curvature in inhibiting lipid-catalyzed fibrillization
A modular synthesis of conformationally preorganised extended β-strand peptidomimetics
Full text linkA promising strategy for mediating protein-protein interactions is the use of non-peptidic mimics of secondary structural protein elements, such as the α-helix. Recent work has expanded the scope of this approach by providing proof-of-principle scaffolds that are conformationally biased to mimic the projection of side-chains from one face of another common secondary structural element-the β-strand. Herein, we present a synthetic route that has key advantages over previous work: monomers bearing an amino acid side-chain were pre-formed before rapid assembly to peptidomimetics through a modular, iterative strategy. The resultant oligomers of alternating pyridyl and six-membered cyclic ureas accurately reproduce a recognition domain of several amino acid residues of a β-strand, demonstrated herein by mimicry of the i, i+2, i+4 and i+6 residues
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