An introduction to NMR titration for studying rapid reversible complexation

Macomber, Roger S.

doi:10.1021/ed069p375

Cited by 164 publications

(109 citation statements)

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“…The formation of 1:1 complexes in the case of 2 allows a straightforward evaluation of anion affinity by NMR titrations (30,35). Not only could the shift of the H(␣) proton be followed in these titrations, but also those of protons in the 3 and 5 positions of the aromatic peptide subunits, whose resonances are also affected by complex formation.…”

Section: Resultsmentioning

confidence: 99%

Conformation and anion binding properties of cyclic hexapeptides containing l -4-hydroxyproline and 6-aminopicolinic acid subunits

Kubik

Goddard

2002

Proc. Natl. Acad. Sci. U.S.A.

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Two cyclic hexapeptides containing alternating all R and all S configured L-(4R͞S)-hydroxyproline and 6-aminopicolinic acid subunits are presented, and the influence of the hydroxyl groups on the solubility, conformation, and receptor properties is investigated. Cyclopeptide 2, containing the natural 4R configured hydroxyproline, adopts a conformation similar to that of the unsubstituted peptide 1, which is able to bind anions such as halides and sulfate in aqueous solution. 2 also interacts with these anions, but whereas 1 forms sandwich type 2:1 complexes, in which the anion is bound by two cyclopeptide moieties, 2 forms 1:1 complexes. The stabilities of the halide and sulfate complexes of 2 range between 10 0 and 10 2 M ؊1 in 80% D2O͞CD3OD. Complex formation is detectable even in water, but with slightly smaller stability constants. Using this information a quantitative evaluation of the stability of the 2:1 complexes of 1, for which overall stability constants in the order 10 4 to 10 5 M ؊2 in 80% D2O͞CD3OD were observed, was made. In contrast to 2, the conformation of 3, containing the non-natural 4S configured hydroxyproline, is strongly affected by the presence of the hydroxyl groups. In d 6-DMSO and methanol͞water mixtures a slow conformational equilibrium between two C3-symmetrical conformers is observed, and 3 is thus much less preorganized for anion binding than either 1 or 2.T he crystal structures of anion binding proteins with the substrate resting in the active site have provided valuable information on the principles nature uses for the recognition of negatively charged compounds (1). Important binding interactions are, for example, multiple hydrogen bonds formed between the substrate and NH groups of the protein backbone or hydrogen bond donors in amino acid side chains (2, 3). A way of mimicking these interactions in an artificial system is to arrange amide or urea NH groups around the cavity of a suitable host molecule. This strategy has led to the development of many artificial hosts for anions, some of which possess remarkable substrate affinity, even in highly competitive solvents such as DMSO or acetonitrile (4-12). The ultimate goal has, of course, been the design of receptors that bind anions by hydrogen bonds in water. However, despite the recent advances in the development of anion receptors (4-7), most systems described so far require strong electrostatic or coordinative interactions to be effective in this solvent. One of the few exceptions is the cyclic hexapeptide 1 that has recently been described by us (13). This neutral macrocyclic receptor interacts with anions such as halides or sulfate even in water͞methanol mixtures, a behavior that can largely be attributed to the special geometry of the complexes formed. We have found that the presence of a suitable anion in solution induces an aggregation of two cyclopeptide molecules, whereby a cavity is formed into which the anion is included (Fig. 1). In this complex, the anion is shielded from the surrounding solvent and can thus inte...

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Section: Resultsmentioning

confidence: 99%

Conformation and anion binding properties of cyclic hexapeptides containing l -4-hydroxyproline and 6-aminopicolinic acid subunits

Kubik

Goddard

2002

Proc. Natl. Acad. Sci. U.S.A.

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“…In the case of the SS peptide titration, chemical shift peak trajectories were fit globally according to Ref. 44 …”

Section: Methodsmentioning

confidence: 99%

Electrostatic Interactions in the Binding Pathway of a Transient Protein Complex Studied by NMR and Isothermal Titration Calorimetry

Meneses

Mittermaier

2014

Journal of Biological Chemistry

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Background: Electrostatic interactions are known accelerate binding in protein complexes with long lifetimes (minutes to hours). Results: NMR and calorimetry were used to characterize binding kinetics in short lived (ϳ1 ms) protein-peptide complexes. Conclusion: Electrostatic enhancement is much less and basal (electrostatic-free) association rates are greater than previously observed. Significance: Electrostatics may play different roles in short lived and long lived protein complexes.

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“…This is clear evidence that the aromatic ring of the DA molecule penetrates the cavity of the sulfonated b-CD. The formation, or association, constant for the inclusion complex was evaluated using the NMR data and a non-linear least square analysis using the relationships, described as follows [25].…”

Section: Nmr Studymentioning

confidence: 99%

A spectrophotometric and NMR study on the formation of an inclusion complex between dopamine and a sulfonated cyclodextrin host

Hendy

Breslin

2011

Journal of Electroanalytical Chemistry

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a b s t r a c tThe formation of an inclusion complex between the sulfonated b-cyclodextrin (Sb-CD) with dopamine (DA) was confirmed using UV-vis measurements and NMR methods. It was also established that a 1:1 complex was formed between the Sb-CD and the DA, where the inclusion occurred predominantly through the aromatic ring of the DA and the hydrophobic CD cavity. The results also suggest that a change in the anion, of supporting electrolyte, had an influence on the DA-Sb-CD complexation while no change was observed for the cation.

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An introduction to NMR titration for studying rapid reversible complexation

Abstract: Nuclear magnetic resonance spectrospcopy is one of the most useful techniques available to chemists for the investigation of dynamic molecular processes.

Cited by 164 publications

References 2 publications

Conformation and anion binding properties of cyclic hexapeptides containing l -4-hydroxyproline and 6-aminopicolinic acid subunits

Conformation and anion binding properties of cyclic hexapeptides containing l -4-hydroxyproline and 6-aminopicolinic acid subunits

Electrostatic Interactions in the Binding Pathway of a Transient Protein Complex Studied by NMR and Isothermal Titration Calorimetry

A spectrophotometric and NMR study on the formation of an inclusion complex between dopamine and a sulfonated cyclodextrin host

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