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Articles 1 - 4 of 4
Full-Text Articles in Physical Sciences and Mathematics
Determining Protease Substrate Selectivity And Inhibition By Label-Free Supramolecular Tandem Enzyme Assays, Garima Ghale, Vijayakumar Ramalingam, Adam R. Urbach, Werner M. Nau
Determining Protease Substrate Selectivity And Inhibition By Label-Free Supramolecular Tandem Enzyme Assays, Garima Ghale, Vijayakumar Ramalingam, Adam R. Urbach, Werner M. Nau
Adam R Urbach
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 high affinity (K ≈ 104 M–1), while their cleavage products (e.g., Phe-Met-NH2) bind very tightly (K …
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
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
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 residues adjacent to N-terminal Trp, Phe, or Tyr. The screen used tetramethylbenzobis(imidazolium) (MBBI) as a fluorescent indicator and resulted in the unexpected discovery that MBBI …
Blind Prediction Of Host-Guest Binding Affinities: A New Sampl3 Challenge, Hari S. Muddana, C Daniel Varnado, Christopher W. Bielawski, Adam R. Urbach, Lyle Isaacs, Matthew T. Geballe, Michael K. Gilson
Blind Prediction Of Host-Guest Binding Affinities: A New Sampl3 Challenge, Hari S. Muddana, C Daniel Varnado, Christopher W. Bielawski, Adam R. Urbach, Lyle Isaacs, Matthew T. Geballe, Michael K. Gilson
Adam R Urbach
The computational prediction of protein–ligand binding affinities is of central interest in early-stage drug-discovery, and there is a widely recognized need for improved methods. Low molecular weight receptors and their ligands—i.e., host–guest systems—represent valuable test-beds for such affinity prediction methods, because their small size makes for fast calculations and relatively facile numerical convergence. The SAMPL3 community exercise included the first ever blind prediction challenge for host–guest binding affinities, through the incorporation of 11 new host–guest complexes. Ten participating research groups addressed this challenge with a variety of approaches. Statistical assessment indicates that, although most methods performed well at predicting some …
Molecular Recognition Of Amino Acids, Peptides, And Proteins By Cucurbit[N]Uril Receptors, Adam R. Urbach, Vijayakumar Ramalingam
Molecular Recognition Of Amino Acids, Peptides, And Proteins By Cucurbit[N]Uril Receptors, Adam R. Urbach, Vijayakumar Ramalingam
Adam R Urbach
At the forefront of the endeavor to understand and manipulate living systems is the design and study of receptors that bind with high affinity and selectivity to specific amino acids, peptides, and proteins. Cucurbit[n]urils are among the most promising class of synthetic receptors for these targets due to their high affinities and selectivities in aqueous media and to the unique combination of electrostatic and hydrophobic interactions that govern binding. The fundamental supramolecular chemistry in this area has been explored in depth, and novel, useful applications are beginning to emerge.