Utilizing Reversible Copper(II) Peptide Coordination in a Sequence‐Selective Luminescent Receptor

Abstract

Although vast information about the coordination ability of amino acids and peptides to metal ions is available, little use of this has been made in the rational design of selective peptide receptors. We have combined a copper(II) nitrilotriacetato (NTA) complex with an ammonium-ion-sensitive and luminescent benzocrown ether. This compound revealed micromolar affinities and selectivities for glycine- and histidine-containing sequences, which closely resembles those of copper(II) ion peptide binding: the two free coordination sites of the copper(II) NTA complex bind to imidazole and amido nitrogen atoms, replicating the initial coordination steps of non-complexed copper(II) ions. The benzocrown ether recognizes the N-terminal amino moiety intramolecularly, and the significantly increased emission intensity signals the binding event, because only if prior coordination of the peptide has taken place is the intramolecular ammonium ion-benzocrown ether interaction of sufficient strength in water to trigger an emission signal. Intermolecular ammonium ion-benzocrown ether binding is not observed. Isothermal titration calorimetry confirmed the binding constants derived from emission titrations. Thus, as deduced from peptide coordination studies, the combination of a truncated copper(II) coordination sphere and a luminescent benzocrown ether allows for the more rational design of sequence-selective peptide receptors.

Aza-27-crown-9 Amino Acid

“…The complete analytics for the intermediates 3 and 4 can be found in the supporting information. -3,5,6,8,9,11,12,13,14,15,17,18,20,21,23,24-hexadecahydro-2H-benzo[k] [1,4,7,10,13,16,19,22,25]octaoxaazacycloheptacosine-27,28-dicarboxylate (6) (a) To a mixture of 0.68 g dimethyl-4,5-dihydroxyphthalate (1) (3 mmol) and 1.38 g K 2 CO 3 (10 mmol) in DMF (5 mL), 3.5 g tetraethyleneglykole monotosylate (2) (10 mmol) in DMF (5 mL) were added and stirred under nitrogen at 60 °C overnight. After cooling to room temperature, the mixture was poured into 30 mL of ice-cold saturated NH 4 Cl solution.…”

“…We have recently developed crown ether amino acids (CEAAs, 21-crown-7) with a luminescent moiety, which bind ammonium ions and indicate the recognition event by changes in their specific emission properties. The units can be covalently linked by peptide coupling to more extended receptors showing high specificity for N-terminal lysine in peptides [4,5] or with other recognition motifs binding for example histidine peptides [6,7]. The ability of benzo-27-crown-9 ethers to bind guanidinium ions is known [8,9], was applied in extraction experiments [10] and has been proven by crystal structures [11,12].…”

Expanding Sapphyrin: Towards Selective Phosphate Binding

“…Stability constants with different tetrabutylammonium salts of inorganic acids were determined by standard 1 H NMR and UV/Vis titration techniques in [D 6 ]DMSO/0.5 % water solution. According to the titration data, receptors containing three pyrrole rings (10 and ties, for example, urea-based (K H 2 PO 4 À/K OAc À = 28 [24] and K H 2 PO 4 À/K OAc À = 232 [25] in [D 6 ]DMSO), amide-based (K H 2 PO 4…”

“…[1][2][3] The range of targets for molecular recognition has dramatically increased in recent years from simple atomic species to more complex structures such as oligopeptides [4,5] and nucleic acids. [6] The binding of phosphate species is of particular interest due to its ubiquitous role in living organisms.…”

Luminescent Lariat Aza-Crown Ether

“…They are versatile building blocks for amino acid and peptide receptors [2][3][4]. Introduction of podand arms [5] may enhance the cation binding affinity of crown ethers [6].…”