NMR‐Solution Structures of Fluoro‐Substituted β‐Peptides: A 314‐Helix and a Hairpin Turn. The First Case of a 90° OCCF Dihedral Angle in an α‐Fluoro‐Amide Group

Mathad, Raveendra I.; Jaun, Bernhard; Flögel, Oliver; Gardiner, James; Löweneck, Markus; Codée, Jeroen D. C.; Seeberger, Peter H.; Seebàch, Dieter; Edmonds, M. K.; Graichen, Florian H. M.; Abell, Andrew D.

doi:10.1002/hlca.200790235

Cited by 55 publications

(26 citation statements)

References 49 publications

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“…All this work is based on an ability to define and control the shape or conformation of peptides. [20][21][22] …”

Section: Resultsmentioning

confidence: 99%

The Influence of Secondary Structure on Electron Transfer in Peptides

Horsley

2013

Aust. J. Chem.

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A series of synthetic peptides containing 0-5 a-aminoisobutyric acid (Aib) residues and a C-terminal redox-active ferrocene was synthesised and their conformations defined by NMR and circular dichroism. Each peptide was separately attached to an electrode for subsequent electrochemical analysis in order to investigate the effect of peptide chain length (distance dependence) and secondary structure on the mechanism of intramolecular electron transfer. While the shorter peptides (0-2 residues) do not adopt a well defined secondary structure, the longer peptides (3-5 residues) adopt a helical conformation, with associated intramolecular hydrogen bonding. The electrochemical results on these peptides clearly revealed a transition in the mechanism of intramolecular electron transfer on transitioning from the ill-defined shorter peptides to the longer helical peptides. The helical structures undergo electron transfer via a hopping mechanism, while the shorter ill-defined structures proceeded via an electron superexchange mechanism. Computational studies on two b-peptides PCB-(b 3 Val-b 3 Ala-b 3 Leu) n -NHC(CH 3 ) 2 OOtBu (n ¼ 1 and 2; PCB ¼ p-cyanobenzamide) were consistent with these observations, where the n ¼ 2 peptide adopts a helical conformation and the n ¼ 1 peptide an ill-defined structure. These combined studies suggest that the mechanism of electron transfer is defined by the extent of secondary structure, rather than merely chain length as is commonly accepted.

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“…All this work is based on an ability to define and control the shape or conformation of peptides. [20][21][22] …”

Section: Resultsmentioning

confidence: 99%

The Influence of Secondary Structure on Electron Transfer in Peptides

Horsley

2013

Aust. J. Chem.

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“…18) [57]. In this more extended system, the stronger propensity for helix formation overrides the conformational influence of the C–F bond, which is forced into a high-energy orientation orthogonal to the adjacent C=O bond.…”

Section: Reviewmentioning

confidence: 99%

The C–F bond as a conformational tool in organic and biological chemistry

Hunter¹

2010

Beilstein J. Org. Chem.

341

173

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SummaryOrganofluorine compounds are widely used in many different applications, ranging from pharmaceuticals and agrochemicals to advanced materials and polymers. It has been recognised for many years that fluorine substitution can confer useful molecular properties such as enhanced stability and hydrophobicity. Another impact of fluorine substitution is to influence the conformations of organic molecules. The stereoselective introduction of fluorine atoms can therefore be exploited as a conformational tool for the synthesis of shape-controlled functional molecules. This review will begin by describing some general aspects of the C–F bond and the various conformational effects associated with C–F bonds (i.e. dipole–dipole interactions, charge–dipole interactions and hyperconjugation). Examples of functional molecules that exploit these conformational effects will then be presented, drawing from a diverse range of molecules including pharmaceuticals, organocatalysts, liquid crystals and peptides.

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“…[33] This may be indicative of some strain imposed by the macrocyclic architecture. [34] To assimilate all of the NMR-derived information described above, we used the Discovery Studio software package to perform conformer searches followed by energy Scheme 1. Synthesis of unguisin A (3) [24] and fluorinated analogues (4-7).…”

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Stereoselective Fluorination Alters the Geometry of a Cyclic Peptide: Exploration of Backbone‐Fluorinated Analogues of Unguisin A

Thomas²,

Griffith

et al. 2014

Angew Chem Int Ed

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New methods for enhancing the efficiency of peptide cyclization, and for fine-tuning the conformations of cyclic peptides, are valuable from a drug development perspective. Herein stereoselective fluorination is investigated as a new strategy for achieving these goals. Four vicinal difluorinated analogues of the natural cyclic heptapeptide unguisin A have been efficiently synthesized. The analogues are found to adopt dramatically different secondary structures, controlled by the fluorine stereochemistry.

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NMR‐Solution Structures of Fluoro‐Substituted β‐Peptides: A 3₁₄‐Helix and a Hairpin Turn. The First Case of a 90° OCCF Dihedral Angle in an α‐Fluoro‐Amide Group

Cited by 55 publications

References 49 publications

The Influence of Secondary Structure on Electron Transfer in Peptides

The Influence of Secondary Structure on Electron Transfer in Peptides

The C–F bond as a conformational tool in organic and biological chemistry

Stereoselective Fluorination Alters the Geometry of a Cyclic Peptide: Exploration of Backbone‐Fluorinated Analogues of Unguisin A

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