6358-69-6Relevant articles and documents
Synthetic catalytic pores
Sakai, Naomi,Sorde, Nathalie,Matile, Stefan
, p. 7776 - 7777 (2003)
Catalytic activity of a synthetic multifunctional pore is studied in large unilamellar vesicles under conditions where substrate and synthetic catalytic pore (SCP) approach the membrane either from the same side (cis catalysis) or from opposite sides (trans catalysis). A synthetic supramolecular rigid-rod β-barrel with excellent ion channel characteristics is identified as SCP using 8-acetoxypyrene-1,3,6-trisulfonate (AcPTS) as model substrate. The key finding is that application of supportive membrane potentials increases the initial velocity of AcPTS esterolysis (v0). This results in an increase of Vmax beyond experimental error (+30%), whereas KM increases less significantly. Long-range electrostatic steering by the membrane potential, possibly guiding substrates into the transmembrane catalyst and, more importantly, accelerating product release (foff = 1.3) is discussed as one possible explanation of this global reduction of catalyst saturation. Control experiments show, inter alia, that similarly strong changes do not occur with opposing membrane potentials. Copyright
Synthesis and activity of histidine-containing catalytic peptide dendrimers
Delort, Estelle,Nguyen-Trung, Nhat-Quang,Darbre, Tamis,Reymond, Jean-Louis
, p. 4468 - 4480 (2006)
Peptide dendrimers built by iteration of the diamino acid dendron Dap-His-Ser (His = histidine, Ser = Serine, Dap = diamino propionic acid) display a strong positive dendritic effect for the catalytic hydrolysis of 8-acyloxypyrene 1,3,6-trisulfonates, which proceeds with enzyme-like kinetics in aqueous medium (Delort, E.; Darbre, T.; Reymond, J.-L. J. Am. Chem. Soc. 2004, 126, 15642-3). Thirty-two mutants of the original third generation dendrimer A3 ((Ac-His-Ser)8(Dap-His-Ser)4(Dap-His-Ser) 2Dap-His-Ser-NH2) were prepared by manual synthesis or by automated synthesis with use of a Chemspeed PSW1100 peptide synthesizer. Dendrimer catalysis was specific for 8-acyloxypyrene 1,3,6-trisulfonates, and there was no activity with other types of esters. While dendrimers with hydrophobic residues at the core and histidine residues at the surface only showed weak activity, exchanging serine residues in dendrimer A3 against alanine (A3A), β-alanine (A3B), or threonine (A3C) improved catalytic efficiency. Substrate binding was correlated with the total number of histidines per dendrimer, with an average of three histidines per substrate binding site. The catalytic rate constant kcat depended on the placement of histidines within the dendrimers and the nature of the other amino acid residues. The fastest catalyst was the threonine mutant A3C ((Ac-His-Thr)8(Dap-His- Thr)4(Dap-His-Thr)2Dap-His-Thr-NH2), with kcat = 1.3 min-1, kcat/kuncat = 90′000, KM = 160 μM for 8-bytyryloxypyrene 1,3,6-trisulfonate, corresponding to a rate acceleration of 18′000 per catalytic site and a 5-fold improvement over the original sequence A3.
A combinatorial approach to catalytic peptide dendrimers
Clouet, Anthony,Darbre, Tamis,Reymond, Jean-Louis
, p. 4612 - 4615 (2004)
Exploring the structural diversity of peptide dendrimers as synthetic protein models: A 65536-membered combinatorial peptide-dendrimer library was prepared by split-and-mix techniques on beads (see picture). The library was screened and revealed peptide dendrimers that catalyze fluorogenic ester hydrolysis and peptide dendrimers that bind to vitamin B12.
A peptide dendrimer enzyme model with a single catalytic site at the core
Javor, Sacha,Delort, Estelle,Darbre, Tamis,Reymond, Jean-Louis
, p. 13238 - 13246 (2007)
Catalytic esterase peptide dendrimers with a core active site were discovered by functional screening of a 65 536-member combinatorial library of third-generation peptide dendrimers using fluorogenic 1-acyloxypyrene-3,6,8- trisulfonates as substrates. In the best catalyst, RMG3, ((AcTyrThr) 8(DapTrpGly)4-(DapArgSerGly)2DapHisSerNH 2), ester hydrolysis is catalyzed by a single catalytic histidine residue at the dendrimer core. A pair of arginine residues in the first-generation branch assists substrate binding. The catalytic proficiency of dendrimer RMG3 (kcat/KM = 860 M-1 min -1 at pH 6.9) per catalytic site is comparable to that of the multivalent esterase dendrimer A3 ((AcHisSer)8(DapHisSer) 4(DapHisSer)2DapHisSerNH2) which has fifteen histidines and five catalytic sites (Delort, E. et al. J. Am. Chem. Soc. 2004, 126, 15642-15643). Remarkably, catalysis in the single site dendrimer RMG3 is enhanced by the outer dendritic branches consisting of aromatic amino acids. These interactions take place in a relatively compact conformation similar to a molten globule protein as demonstrated by diffusion NMR. In another dendrimer, HG3 ((AcllePro)8(DaplleThr)4(DapHisAla) 2DapHisLeuNH2) by contrast, catalysis by a core of three histidine residues is unaffected by the outer dendritic layers. Dendrimer HG3 or its core HG1 exhibit comparable activity to the first-generation dendrimer A1 ((AcHisSer)2DapHisSerNH2). The compactness of dendrimer HG3 in solution is close to that a denatured peptide. These experiments document the first esterase peptide dendrimer enzyme models with a single catalytic site and suggest a possible relationship between packing and catalysis in these systems.
Triggered Release from Lipid Bilayer Vesicles by an Artificial Transmembrane Signal Transduction System
Langton, Matthew J.,Scriven, Lorel M.,Williams, Nicholas H.,Hunter, Christopher A.
, p. 15768 - 15773 (2017/11/14)
The on-demand delivery of drug molecules from nanoscale carriers with spatiotemporal control is a key challenge in modern medicine. Here we show that lipid bilayer vesicles (liposomes) can be triggered to release an encapsulated molecular cargo in response to an external control signal by employing an artificial transmembrane signal transduction mechanism. A synthetic signal transducer embedded in the lipid bilayer membrane acts as a switchable catalyst, catalyzing the formation of surfactant molecules inside the vesicle in response to a change in external pH. The surfactant permeabilizes the lipid bilayer membrane to facilitate release of an encapsulated hydrophilic cargo. In the absence of the pH control signal, the catalyst is inactive, and the cargo remains encapsulated within the vesicle.
Enzyme-artificial enzyme interactions as a means for discriminating among structurally similar isozymes
Selvakumar, Karuthapandi,Motiei, Leila,Margulies, David
supporting information, p. 4892 - 4895 (2015/05/05)
We describe the design and function of an artificial enzyme-linked receptor (ELR) that can bind different members of the glutathione-S-transferase (GST) enzyme family. The artificial enzyme-enzyme interactions distinctly affect the catalytic activity of the natural enzymes, the biomimetic, or both, enabling the system to discriminate among structurally similar GST isozymes.
