15 Works

Effects of sequence context on the binding of tryptophan-containing peptides by the cucurbit[8]uril–methyl viologen complex

Omar A. Ali, Eric M. Olson & Adam R. Urbach
(2013). Effects of sequence context on the binding of tryptophan-containing peptides by the cucurbit[8]uril–methyl viologen complex. Supramolecular Chemistry: Vol. 25, No. 12, pp. 863-868.

Multivalent Recognition of Peptides by Modular Self-Assembled Receptors

Adam R. Urbach, Joseph J. Reczek, Aimee A. Kennedy & Brian T. Halbert
Developing nontraditional approaches to the synthesis and characterization of multivalent compounds is critical to our efforts to study and interface with biological systems and to build new noncovalent materials. This paper demonstrates a biomimetic approach to the construction of discrete, modular, multivalent receptors via molecular self-assembly in aqueous solution. Scaffolds presenting 1−3 viologen groups recruit a respective 1−3 copies of the synthetic host, cucurbit[8]uril, in a noncooperative manner and with a consistent equilibrium association constant...

Cucurbit[8]uril Rotaxanes

Adam R. Urbach & Vijayakumar Ramalingam
The synthesis of [2]rotaxanes, each comprising a viologen core threaded through a cucurbit[8]uril (Q8, Figure 1) macrocycle and stoppered by tetraphenylmethane groups, and their binding to second guests as inclusion complexes in organic and aqueous media are described. Stoppering was observed to have little effect on binding. Chemical modification of the threaded guest was used to control solubility and binding characteristics, thus demonstrating a novel approach to making artificial receptors with readily modifiable properties.

Life history and environment predict variation in testosterone across vertebrates

Jerry Husak, Matthew Fuxjager, Michele A. Johnson, Maren Vitousek, Jeremy Donald, Clinton David Francis, Wolfgang Goymann, Michaela Hau, Bonnie Kircher, Rosemary Knapp, Lynn B. Martin, Eliot Miller, Laura Schoenle & Tony Williams
Endocrine systems act as key intermediaries between organisms and their environments. This interaction leads to high variability in hormone levels, but we know little about the ecological factors that influence this variation within and across major vertebrate groups. We study this topic by assessing how various social and environmental dynamics influence testosterone levels across the entire vertebrate tree of life. Our analyses show that breeding season length and mating system are the strongest predictors of...

Charge-Mediated Recognition of N-Terminal Tryptophan in Aqueous Solution by a Synthetic Host

Adam R. Urbach, Meghan E. Bush & Nicole D. Bouley
The molecular recognition of peptides and proteins in aqueous solution by designed molecules remains an elusive goal with broad implications for basic biochemical research and for sensors and separations technologies. This paper describes the recognition of N-terminal tryptophan in aqueous solution by the synthetic host cucurbit[8]uril (Q8). Q8 is known to form 1:1:1 heteroternary complexes with methyl viologen (MV) and a second aromatic guest. Here, the complexes of Q8·MV with (i) the four natural aromatic...

Molecular Recognition of Methionine-Terminated Peptides by Cucurbit[8]uril

Zoheb Hirani, Hailey F. Taylor, Emily F. Babcock, Andrew T. Bockus, C. Daniel Varnado, Christopher W. Bielawski & Adam Urbach
This Article describes the molecular recognition of peptides containing an N-terminal methionine (Met) by the synthetic receptor cucurbit[8]uril (Q8) in aqueous solution and with submicromolar affinity. Prior work established that Q8 binds with high affinity to peptides containing aromatic amino acids, either by simultaneous binding of two aromatic residues, one from each of two different peptides, or by simultaneous binding of an aromatic residue and its immediate neighbor on the same peptide. The additional binding...

Sequence-Specific Recognition and Cooperative Dimerization of N-Terminal Aromatic Peptides in Aqueous Solution by a Synthetic Host

Adam R. Urbach, Alexander B. Taylor, P. John Hart & Lisa M. Heitmann
This article describes the selective recognition and noncovalent dimerization of N-terminal aromatic peptides in aqueous solution by the synthetic host compound, cucurbit[8]uril (Q8). Q8 is known to bind two aromatic guests simultaneously and, in the presence of methyl viologen, to recognize N-terminal tryptophan over internal and C-terminal sequence isomers. Here, the binding of Q8 to aromatic peptides in the absence of methyl viologen was studied by isothermal titration calorimetry (ITC), 1H NMR spectroscopy, and X-ray...

Nanomolar Binding of Peptides Containing Noncanonical Amino Acids by a Synthetic Receptor

Leigh A. Logsdon, Christopher L. Schardon, Vijayakumar Ramalingam, Sharon K. Kwee & Adam R. Urbach
This paper describes the molecular recognition of phenylalanine derivatives and their peptides by the synthetic receptor cucurbit[7]uril (Q7). The 4-tert-butyl and 4-aminomethyl derivatives of phenylalanine (tBuPhe and AMPhe) were identified from a screen to have 20–30-fold higher affinity than phenylalanine for Q7. Placement of these residues at the N-terminus of model tripeptides (X-Gly-Gly), resulted in no change in affinity for tBuPhe-Gly-Gly, but a remarkable 500-fold increase in affinity for AMPhe-Gly-Gly, which bound to Q7 with...

Cucurbit[7]uril–Tetramethylrhodamine Conjugate for Direct Sensing and Cellular Imaging

Lyle Isaacs, Andrew T. Bockus, Adam Urbach, Omar A. Ali, Lauren Smith, Amy G. Grice, Carolyn C. Young, William Mobley, Ashley Leek, James L. Roberts & Brittany Vinciguerra
This paper describes the design and synthesis of a conjugate (Q7R) comprising the synthetic host cucurbit[7]uril (Q7) linked to the fluorescent dye tetramethylrhodamine (TMR), and the characterization of its optical and guest-binding properties as well as its cellular uptake. Q7R was synthesized in two steps from monofunctionalized azidobutyl-Q7 and NHS-activated TMR. The fluorescence of Q7R is quenched upon guest binding, and this observable was used to determine equilibrium dissociation constant (Kd) values. Unexpectedly, the Kd...

Benzobis(imidazolium)-Cucurbit[8]uril Complexes for Binding and Sensing Aromatic Compounds in Aqueous Solution

Frank Biedermann, Urs Rauwald, Monika Cziferszky, Kyle A. Williams, Lauren D. Gann, Bi Y. Guo, Adam R. Urbach, Christopher W. Bielawski & Oren A. Scherman
Abstract The utilities of benzobis(imidazolium) salts (BBIs) as stable and fluorescent components of supramolecular assemblies involving the macrocyclic host, cucurbit[8]uril (CB[8]), are described...

Sequence-Specific, Nanomolar Peptide Binding via Cucurbit[8]uril-Induced Folding and Inclusion of Neighboring Side Chains

Lauren C. Smith, David G. Leach, Brittney E. Blaylock, Omar A. Ali & Adam R. Urbach
This paper describes the molecular recognition of the tripeptide Tyr-Leu-Ala by the synthetic receptor cucurbit[8]uril (Q8) in aqueous buffer with nanomolar affinity and exceptional specificity. This combination of characteristics, which also applies to antibodies, is desirable for applications in biochemistry and biotechnology but has eluded supramolecular chemists for decades. Building on prior knowledge that Q8 binds to peptides with N-terminal aromatic residues, a library screen of 105 peptides was designed to test the effects of...

Molecular Recognition of Insulin by a Synthetic Receptor

Jordan M. Chinai, Alexander B. Taylor, Lisa M. Ryno, Nicholas D. Hargreaves, Christopher A. Morris, P. John Hart & Adam R. Urbach
The discovery of molecules that bind tightly and selectively to desired proteins continues to drive innovation at the interface of chemistry and biology. This paper describes the binding of human insulin by the synthetic receptor cucurbit[7]uril (Q7) in vitro. Isothermal titration calorimetry and fluorescence spectroscopy experiments show that Q7 binds to insulin with an equilibrium association constant of 1.5 × 106 M−1 and with 50−100-fold selectivity versus proteins that are much larger but lack an...

Effects of the number and placement of positive charges on viologen–cucurbit[n]uril interactions

Adam R. Urbach & Gretchen A. Vincil
(2008). Effects of the number and placement of positive charges on viologen–cucurbit[n]uril interactions. Supramolecular Chemistry: Vol. 20, No. 8, pp. 681-687.

Determining Protease Substrate Selectivity and Inhibition by Label-Free Supramolecular Tandem Enzyme Assays

Garima Ghale, Vijayakumar Ramalingam, Adam R. Urbach & Werner M. Nau
An analytical method has been developed for the continuous monitoring of protease activity on unlabeled peptides in real time by fluorescence spectroscopy. The assay is enabled by a reporter pair comprising the macrocycle cucurbit[7]uril (CB7) and the fluorescent dye acridine orange (AO). CB7 functions by selectively recognizing N-terminal phenylalanine residues as they are produced during the enzymatic cleavage of enkephalin-type peptides by the metalloendopeptidase thermolysin. The substrate peptides (e.g., Thr-Gly-Ala-Phe-Met-NH2) bind to CB7 with moderately...

Sequence-Specific Inhibition of a Nonspecific Protease

Leigh A. Logsdon & Adam R. Urbach
A nonspecific exopeptidase, aminopeptidase N (APN), is inhibited sequence-specifically by a synthetic host, cucurbit[7]uril (Q7), which binds with high affinity and specificity to N-terminal phenylalanine (Phe) and 4-(aminomethyl)phenylalanine (AMPhe) and prevents their removal from the peptide. Liquid chromatography experiments demonstrated that in the presence of excess Q7, APN quantitatively converts the pentapeptides Thr-Gly-Ala-X-Met into the dipeptides X-Met (X = Phe, AMPhe). The resulting Q7-bound products are completely stable to proteolytic digestion for at least 24...

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