Substrate Catalysis Research Articles

Structural basis for membrane association and catalysis by phosphatidylserine synthase in Escherichia coli.

Phosphatidylserine synthase (PssA) is essential in the biosynthesis of phosphatidylethanolamine, a major phospholipid of bacterial membranes. A peripheral membrane protein PssA can associate with the cellular membrane in its active state or exist in the cytosol in an inactive form. The membrane-bound enzyme acts on cytidine diphosphate diacylglycerol (CDP-DG) to form cytidine monophosphate and a covalent intermediate, which is subsequently targeted by serine to produce phosphatidylserine. Here, we present two crystal structures of Escherichia coli PssA, one complexed with CDP-DG and the other without. The lipid-bound structure mimics the Michaelis complex before the formation of a covalent intermediate, revealing key determinants for substrate recognition and catalysis. Notably, membrane-free PssA is in a monomer-dimer equilibrium, with only the monomer capable of associating with the membrane, suggesting a regulatory mechanism for phospholipid biosynthesis dependent on the oligomerization state of the enzyme.

Engineered β1-3-N-Acetylglucosaminyltransferase Facilitating the One-Pot Multienzyme Synthesis of Human Milk Oligosaccharides.

β1-3-linked N-acetylglucosaminide is a prevalent carbohydrate motif found in oligosaccharides, polysaccharides, glycoproteins, and glycolipids. It is a crucial component of human milk oligosaccharides (HMOs). Neisseria meningitidis β1-3-N-acetylglucosaminyltransferase (NmLgtA) catalyzes the formation of a glycosidic bond and has the potential for use in synthesizing HMOs. However, this application is hindered by challenges such as low levels of enzyme expression, poor stability, and significant aggregation. Since there is no available crystal structure for NmLgtA, we used its AlphaFold 2 predicted structure to identify potential unfavorable factors. We then modified the enzyme by removing the 17 N-terminal amino acids and substituting nine specific residues. The engineered NmLgtA-Opti exhibited improved thermal stability, increased soluble protein expression, complete relief from aggregation, and enhanced catalysis while maintaining its catalytic specificity and substrate promiscuity. Furthermore, NmLgtA-Opti maximizes substrate utilization and can be employed in a sequential one-pot multienzyme platform for high-yield production of HMOs.

High-Throughput Screening Approach for Catalytic Applications through Regulation of Adsorption Energies via Work Function.

Adsorption energy is critical in catalysis, energy storage, and sensing. Optimal adsorption energy on a catalytic substrate is essential as extreme adsorption energy can reduce the reaction efficiency. Building on our previous research on the influence of work function on adsorption energy (Phys. Chem. Chem. Phys. 2024, 26, 3525-3530), we examined a range of two-dimensional semiconductor materials, including black phosphorene, boron nitride, and MoS2, as supporting substrates for the construction of silicene-semiconductor heterojunctions. Furthermore, we analyzed how work function changes impact adsorption energy during O2 adsorption and developed a theoretical model to explain this relationship. The model was validated by demonstrating the regulation of the catalytic reaction barrier in the oxygen reduction reaction and was applied to N2 adsorption via high-throughput screening. Our findings demonstrate that the work function modulates the adsorption energy in van der Waals heterojunctions, enhancing catalytic efficiency. This approach aligns with the Sabatier principle and offers a pathway for optimizing catalysts.

Oxygen-boosted fluorinated prodrug hybrid nanoassemblies for bidirectional amplification of breast cancer ferroptosis

Ferroptosis, a novel form of cell death, has emerged as a promising approach in cancer therapy. However, the single ferroptosis inducer was ineffective, and the induction of ferroptosis was severely limited by hypoxia niches in breast cancer. Herein, we develop a disulfide bond-bridging fluorinated doxorubicin (DOX) prodrug, which can facilitate the formation of hybrid nanoassemblies (NAs) with sorafenib (Sor) through a molecular co-assembly strategy. The incorporation of fluorinated side chains enhances the oxygen-carrying capacity of the NAs, successfully reversing the redox offensive and defensive situation caused by the dilemma of hypoxia. The reactive oxygen species (ROS) generation capacity of DOX via nicotinamide adenine dinucleotide oxidase (NOXs) within hypoxic tumors is significantly enhanced due to the presence of fluorinated oxygen-carrying as a catalytic substrate. Furthermore, the depletion of nicotinamide adenine dinucleotide phosphate (NADPH) significantly impairs the synthesis of glutathione (GSH), which collaboratively inhibits GSH production with Sor. As expected, the NAs with bidirectional amplification of ROS production and GSH inhibition displays potent antitumor activity in 4 T1 breast cancer-bearing mice. Together, this study presents a novel nanotherapeutic approach for ferroptosis-driven tumor therapy.

Systematic characterization of cinnamyl alcohol dehydrogenase members revealed classification and function divergence in Haplomitrium mnioides.

Cinnamyl alcohol dehydrogenase (CAD; EC 1.1.1.195) is considered to be a key enzyme in lignin biosynthesis, which can catalyze cinnamyl aldehyde to produce cinnamyl alcohol. In this study, three putative CADs were characterized from the liverwort Haplomitrium mnioides. The sequence alignment and phylogenetic analysis revealed that HmCADs belonged to a multigene family, with three HmCADs belonging to class II, class III, and class IV, respectively. In vitro enzymatic studies demonstrated that HmCAD2 exhibited high affinity and catalytic activity towards five cinnamyl aldehydes, followed by HmCAD3 with poor catalytic activity, and HmCAD1 catalyzed only the reaction of p-coumaryl aldehyde and coniferyl aldehyde with extremely low catalytic capacity. Protein-substrate binding simulations were performed to investigate the differences in catalytic activity exhibited when proteins catalyzed different substrates. Furthermore, distinct expression patterns of three HmCADs were identified in different plant tissues. Subcellular localization tests confirmed that HmCAD1/2/3 was located in the cytoplasm. The simulated responses of HmCADs to different stresses showed that HmCAD1 played a positive role in coping with each stress, while HmCAD2/3 was weak. These findings demonstrate the diversity of CADs in liverwort, highlight the divergent role of HmCAD1/2/3 in substrate catalysis, and also suggest their possible involvement in stress response, thereby providing new insights into CAD evolution while emphasizing their potential distinctive and collaborative contributions to the normal growth of primitive liverworts.

Au/CeO2 Nanozyme Scaffold Boosts Electron and Hydrogen Transfer for NIR-Enhanced Chemodynamic Therapy.

CeO2 nanozymes have demonstrated the potential to enhance biological scaffolds with chemodynamic therapy. However, their catalytic efficacy is limited by the slow conversion of Ce4+ to Ce3+ and the lack of substrates like H2O2 and H+. To address these challenges, we adopted a dual-pronged strategy that utilized the plasmonic resonance of Au nanoparticles and their glucose-oxidase mimicry to boost electron and hydrogen transfer. Specifically, we integrated Au/CeO2 nanozymes into poly-l-lactic acid scaffolds via selective laser sintering. This conversion of Ce3+ to Ce4+ in the scaffolds enhanced the reduction of H2O2 to a hydroxyl radical, inducing oxidative stress in tumor cells. The Au nanoparticles played a crucial role in boosting the Ce3+/Ce4+ catalytic cycle by providing both the energy and the catalytic substrates. They recycled Ce4+ back to Ce3+ by exploiting plasmonic-induced hot electrons and catalyzed glucose oxidation to supply H2O2 and H+. Our nanoscale and atomic-scale simulations confirmed that the Au/CeO2 hybrid structure utilized near-field coupling to amplify the plasmonic resonance and the Au-O-Ce bridge reduced the electron transfer barrier. Consequently, the Au/CeO2 scaffold decreased the activation energy from 22.57 to 9.92 kJ/mol. These findings highlight the significant promise of the Au/CeO2 nanozyme scaffold for NIR-enhanced chemodynamic therapy.

Unraveling the Molecular Determinants of Catalytic Efficiency and Substrate Specificity in l-Amino Acid Decarboxylases.

l-Tryptophan decarboxylase (TDC) and l-3,4-dihydroxyphenylalanine decarboxylase (DDC) catalyze the decarboxylation of l-tryptophan, 5-hydroxytryptophan, and l-3,4-dihydroxyphenylalanine. In this study, we analyzed the amino acid compositions of the substrate-binding pockets of TDC from Catharanthus roseus (CrTDC) and DDC from Sus scrofa (SsDDC), explored the specificity of key amino acids within these pockets, and elucidated mechanisms influencing substrate selectivity and catalytic activity in both enzymes, using whole-cell catalysis to screen mutants and determine enzymatic kinetic parameters. The results demonstrated that residues Ala-103 and Val-122 in CrTDC, along with their corresponding sites Thr-82 and Ile-101 in SsDDC, significantly influence substrate selectivity and catalytic efficiency. Molecular dynamics simulations revealed that substrate selectivity and catalytic efficiency depends on the nucleophilic attack distance between the substrate's amino group and the C4' of pyridoxal 5'-phosphate. This study elucidates the catalytic mechanisms and structural bases of TDC and DDC, guiding enhancements in the related aromatic monoamine biosynthesis.

Expression of the polyphenol oxidase gene MdPPO7 is modulated by MdWRKY3 to regulate browning in sliced apple fruit.

Browning is a pervasive problem in horticultural products, substantially diminishing the appearance, flavor and nutritional value of fruit, including important fruits like apple (Malus × domestica Borkh.). In this study, we compared the physiological characteristics of the browning-resistant line 'Rb-18' with the susceptible variety 'Fuji' and found that the polyphenol oxidase (PPO) enzyme activity and phenolic content of Rb-18 were significantly lower than those in Fuji. In addition, the PPO enzyme in Fuji showed a stronger affinity for its substrate, catechol, compared to Rb-18. Through transcriptome and RT-qPCR analyses, MdPPO7 expression was identified as contributing to flesh browning after cutting. Subsequent fruit injection and stable genetic transformation of the MdPPO7 gene into apple fruit and calli determined that syringic acid, procyanidin, phloridzin, chlorogenic acid, gallic acid, catechin, and caffeic act as its catalytic substrates in the process involved in browning. Furthermore, luciferase reporter, yeast one-hybrid, β-glucuronidase reporter assays and chip-qPCR analysis demonstrated that a WRKY transcription factor(MdWRKY3) binds to the promoter region of polyphenol oxidase gene (MdPPO7) and positively regulates its expression to promote apple flesh browning. This study provides insights into the molecular regulatory mechanisms of fruit browning in fresh-cut apples and provides a theoretical basis for the generation of high-quality apple germplasm resources.

Examining prestructured β-actin peptides as substrates of histidine methyltransferase SETD3

The Nτ-His73 methylation of β-actin by histidine methyltransferase SETD3 is required for the integrity of the cellular cytoskeleton. Modulation of SETD3 activity in human cells facilitates cancer-like changes to the cell phenotype. SETD3 binds β-actin in an extended conformation, with a conserved bend-like motif surrounding His73. Here, we report on the catalytic specificity of SETD3 towards i, i + 3 stapled β-actin peptides possessing a limited conformational freedom surrounding the His73 substrate residue via positions Glu72 and Ile75. Stapled β-actin peptides were observed to be methylated less efficiently than the linear β-actin peptide. None of the stapled β-actin peptides efficiently inhibited the SETD3-catalyzed Nτ-His73 methylation reaction. Molecular dynamics simulations demonstrated that the unbound and SETD3-bound β-actin peptides display different backbone flexibility and bend-like conformations, highlighting their important role in substrate binding and catalysis. Overall, these findings suggest that reduced backbone flexibility of β-actin prevents the formation of optimal protein-peptide interactions between the enzyme and substrate, highlighting that the backbone flexibility needs to be considered when designing β-actin-based probes and inhibitors of biomedically important SETD3.

CIGB-300 internalizes and impairs viability of NSCLC cells lacking actionable targets by inhibiting casein kinase-2 signaling

Overall response rates in advanced Non-Small Cell Lung Cancer (NSCLC) remains low. Thus, novel molecular targets, tailored drugs and/or drug combinations are needed. Casein Kinase-2 (CK2) is a constitutively active and frequently over-expressed enzyme which fosters tumor survival, proliferation and metastasis. By using a clinical-grade and Cell Penetrating Peptide-based inhibitor coined as CIGB-300, we explore the anti-neoplastic effects caused by interruption of CK2 signaling in lung cancer cells lacking EGFR, ALK and ROS mutations. CIGB-300 penetrated and impaired viability and proliferation of Lung Adenocarcinoma (LUAD) (A549, NCI-H522) and Lung Squamous Carcinoma (LUSC) (NCI-H226 and SK-MES-1) cells in a dose-response manner. The differential activity could not be explained by overall peptide uptake or its subcellular distribution, as evidenced by flow cytometry and confocal microscopy. Upon internalization, CIGB-300 interacted with CK2 catalytic subunits (ɑ1/ɑ2) and CK2 substrates, thus impairing phosphorylation of enzyme substrates (CDC37s13, NPM1s125) and downstream proteins (RPS6s325/326). CK2 inhibition induced an early Reactive Oxygen Species (ROS) and mitochondrial membrane depolarization, which predates lung cancer cell death. Finally, intravenous injection of CIGB-300 in a cell line-based xenograft corroborated CIGB-300’s anti-tumor effects and suggested concurrent in situ reductions of CSNK2ɑ subunit and downstream RPS6s235/236 phosphorylation. Overall, CIGB-300 therapeutic hypothesis and antineoplastic effects demonstrated herein, further support the evaluation of this clinical-grade CK2 inhibitor in advanced NSCLC with limited therapeutic options.

Substrate binding and catalytic mechanism of UDP-α-D-galactofuranose: β-galactofuranoside β-(1→5)-galactofuranosyltransferase GfsA.

UDP-α-D-galactofuranose (UDP-Galf): β-galactofuranoside β-(1→5)-galactofuranosyltransferase, known as GfsA, is essential in synthesizing β-(1→5)-galactofuranosyl oligosaccharides that are incorporated into the cell wall of pathogenic fungi. This study analyzed the structure and function of GfsA from Aspergillus fumigatus. To provide crucial insights into the catalytic mechanism and substrate recognition, the complex structure was elucidated with manganese (Mn2+), a donor substrate product (UDP), and an acceptor sugar molecule (β-galactofuranose). In addition to the typical GT-A fold domain, GfsA has a unique domain formed by the N and C termini. The former interacts with the GT-A of another GfsA, forming a dimer. The active center that contains Mn2+, UDP, and galactofuranose forms a groove structure that is highly conserved in the GfsA of Pezizomycotina fungi. Enzymatic assays using site-directed mutants were conducted to determine the roles of specific active-site residues in the enzymatic activity of GfsA. The predicted enzyme-substrate complex model containing UDP-Galf characterized a specific β-galactofuranosyltransfer mechanism to the 5'-OH of β-galactofuranose. Overall, the structure of GfsA in pathogenic fungi provides insights into the complex glycan biosynthetic processes of fungal pathogenesis and may inform the development of novel antifungal therapies.

Structural insights into the inhibition mechanism of fungal GWT1 by manogepix

Glycosylphosphatidylinositol (GPI) acyltransferase is crucial for the synthesis of GPI-anchored proteins. Targeting the fungal glycosylphosphatidylinositol acyltransferase GWT1 by manogepix is a promising antifungal strategy. However, the inhibitory mechanism of manogepix remains unclear. Here, we present cryo-EM structures of yeast GWT1 bound to the substrate (palmitoyl-CoA) and inhibitor (manogepix) at 3.3 Å and 3.5 Å, respectively. GWT1 adopts a unique fold with 13 transmembrane (TM) helixes. The palmitoyl-CoA inserts into the chamber among TM4, 5, 6, 7, and 12. The crucial residues (D145 and K155) located on the loop between TM4 and TM5 potentially bind to the GPI precursor, contributing to substrate recognition and catalysis, respectively. The antifungal drug, manogepix, occupies the hydrophobic cavity of the palmitoyl-CoA binding site, suggesting a competitive inhibitory mechanism. Structural analysis of resistance mutations elucidates the drug specificity and selectivity. These findings pave the way for the development of potent and selective antifungal drugs targeting GWT1.

Open frame-like Co-Fe oxides superstructures for highly efficient cross-dehydrogenative coupling reaction of N-phenyltetrahydroisoquinoline under mild conditions

An open frame-like Co-Fe oxides catalyst has been successfully prepared using a time-controlled strategy. Benefiting from the unique open frame-like superstructure and synergistic bimetallic composition, this novel catalyst exhibits excellent catalytic activity (up to 91 % isolated yield) and substrate suitability for Cross-Dehydrogenative Coupling reaction (CDC) of N-phenyltetrahydroisoquinolines and nitroalkanes using oxygen as the oxidant under mild reaction conditions. And after several runs, the reused catalyst still maintains great stability. This may attributed to the interaction between Fe and Co. In addition, through the radical trapping experiments, we found that O2·− species play an important role in the cross-dehydrogenative coupling reaction.

Functional identification of carbohydrate-binding module 13 and its application to quantification of hemicellulose in gramineous plants

Gramineous biomass is a type of lignocellulose commonly used as a renewable energy source. Accurate quantification of hemicellulose within this biomass is crucial for its efficient conversion. Carbohydrate-binding modules (CBMs) help catalytic domains anchor substrates, representing the potential to be developed as fluorescence probes for hemicellulose content determination. In this study, we discovered a CBM named EmCBM13, derived from the bifunctional enzyme Xyn10A/Fae1A within the bacterial consortium EMSD5. This CBM displays a remarkable ability to bind soluble and insoluble hemicellulose components of gramineous plants. Through molecular docking and mutational analysis, we pinpointed two essential tyrosine residues mediating ligand interaction of EmCBM13. Leveraging the binding characteristics of EmCBM13, we created a fluorescence probe called EmCBM13-GFP by fusing a GFP with EmCBM13. We observed a positive correlation between the fluorescence contents of EmCBM13-GFP bound to hemicellulose and the hemicellulose contents in various gramineous biomasses. Utilizing this correlation, we rapidly determined the hemicellulose content in different gramineous plants with 90–110 % accuracy. This probe shows promise in quickly evaluating the characteristics of gramineous biomass feedstock for research and production purposes.

Catalytic activities of wild-type C. elegans DAF-2 kinase and dauer-associated mutants.

DAF-2, the Caenorhabditis elegans insulin-like receptor homolog, regulates larval development, metabolism, stress response, and lifespan. The availability of numerous daf-2 mutant alleles has made it possible to elucidate the genetic mechanisms underlying these physiological processes. The DAF-2 pathway is significantly conserved with the human insulin/IGF-1 signaling pathway; it includes proteins homologous to human IRS, GRB-2, and PI3K, making it an important model to investigate human pathological conditions. We expressed and purified the kinase domain of wild-type DAF-2 to examine the catalytic activity and substrate specificity of the enzyme. Like the human insulin receptor kinase, DAF-2 kinase phosphorylates tyrosines within specific YxN or YxxM motifs, which are important for recruiting downstream effectors. DAF-2 kinase phosphorylated peptides derived from the YxxM and YxN motifs located in the C-terminal extension of the receptor tyrosine kinase, consistent with the idea that the DAF-2 receptor may possess independent signaling capacity. Unlike the human insulin or IGF-1 receptor kinases, DAF-2 kinase was poorly inhibited by the small-molecule inhibitor linsitinib. We also expressed and purified mutant kinases corresponding to daf-2 alleles that result in partial loss-of-function phenotypes in C. elegans. These mutations caused a complete loss of kinase function in vitro. Our biochemical investigations provide new insights into DAF-2 kinase function, and the approach should be useful for studying other mutations to shed light on DAF-2 signaling in C. elegans physiology.

Vitis vinifera Lipoxygenase LoxA is an Allosteric Dimer Activated by Lipidic Surfaces

Lipoxygenases catalyze the peroxidation of poly-unsaturated fatty acid chains either free or esterified in membrane lipids. Vitis vinifera LoxA is transcriptionally induced at ripening onset and localizes at the inner chloroplastic membrane where it is responsible for galactolipid regiospecific mono- and di-peroxidation. Here we present a kinetic and structural characterization of LoxA. Our X-ray structures reveal a constitutive dimer with detergent induced conformational changes affecting substrate binding and catalysis. In a closed conformation, a LID domain prevents substrate access to the catalytic site by steric hindrance. Detergent addition above the CMC destabilizes the LID and opens the dimer with both catalytic sites accessible from the same surface framed by the PLAT domains. As a consequence, detergent molecules occupy allosteric sites in the PLAT/catalytic domain interfaces. These structural changes are mirrored by increased enzymatic activity and positive cooperativity when the substrate is provided in micelles. The ability to interact with micelles is lost upon dimer destabilization by site-directed mutagenesis as assessed by tryptophan fluorescence. Our data allow to propose a model for protein activation at the membrane, classifying LoxA as an interfacial enzyme acting on fatty acid chains directly from the membrane similar to mammalian 15-LOX and 5-LOX.

Challenges and perspectives in using unspecific peroxygenases for organic synthesis

In the past 20 years, unspecific peroxygenases (UPOs) have emerged as promising biocatalysts for various organic transformations. Particularly, we have witnessed great attention being paid to the screening of new enzymes and expansion of the substrates/products. However, challenges such as enzyme stability, low turnover numbers, and substrate specificity hinder their widespread utilization in practical organic synthesis. This review article provides a concrete and mini-overview of the challenges associated with using UPOs in organic synthesis and discusses strategies for enzyme engineering to overcome these limitations. The article highlights recent advancements in UPO research and presents potential solutions to enhance their catalytic efficiency, stability, substrate specificity, and regioselectivity. Additionally, the review outlines the current methodologies employed for directed evolution and protein engineering of UPOs, along with computational modeling approaches for rational enzyme design. By addressing the challenges and exploring avenues for enzyme engineering, this review aims to shed light on the prospects of UPOs in organic synthesis.

"All-in-One" MnO2@PtAuRu Nanoreactor for Self-Replenishing and Cascade Catalytic Therapy of Cancer.

Limited by the insufficient catalytic substrates such as H2O2 and O2 in the tumor microenvironment (TME), the continual propelling of nanozymes catalysis therapy of cancer remains a challenge. Here, an all-in-one MnO2@PtAuRu nanoreactor is constructed for self-propelled and cascade catalytic therapy of tumors. The MnO2@PtAuRu is constructed by using hollow MnO2 (≈150nm) as the core-carrier and ultrasmall PtAuRu nanoclusters (≈2nm) anchoring on the surface MnO2. According to the glucose oxidase (GOD)/catalase (CAT)/peroxidase (POD) mimic multienzyme activity of PtAuRu nanoclusters, cascaded nanocatalytic reactions can be self-replenishing to persistently produce •OH for superior chemodynamic therapy (CDT). Additionally, the MnO2 carrier can protect the ultrasmall PtAuRu nanoclusters during the circulation and the overexpressed glutathione (GSH) in the tumor can also be degraded by the MnO2 to synergy the CDT. The MnO2@PtAuRu displays obvious photothermal properties which further enhance the cascade catalytic ability and synergistic therapeutic effect. Therefore, this all-in-one nanozyme provides a promising strategy for the rational design of self-replenishment and self-replenishing cascade catalytic therapy of cancer.

An in vitro platform for the enzymatic characterization of the rhomboid protease RHBDL4.

Rhomboid proteases are ubiquitous intramembrane serine proteases that can cleave transmembrane substrates within lipid bilayers. They exhibit many and diverse functions, such as but not limited to, growth factor signaling, immune and inflammatory response, protein quality control, and parasitic invasion. Human rhomboid protease RHBDL4 has been demonstrated to play a critical role in removing misfolded proteins from the Endoplasmic Reticulum and is implicated in severe diseases such as various cancers and Alzheimer's disease. Therefore, RHBDL4 is expected to constitute an important therapeutic target for such devastating diseases. Despite its critical role in many biological processes, the enzymatic properties of RHBDL4 remain largely unknown. To enable a comprehensive characterization of RHBDL4's kinetics, catalytic parameters, substrate specificity, and binding modality we expressed and purified recombinant RHBDL4, and employed it in a Förster Resonance Energy Transfer-based cleavage assay. Until now, kinetic studies have been limited mostly to bacterial rhomboid proteases. Our in vitro platform offers a new method for studying RHBDL4's enzymatic function and substrate preferences. Furthermore, we developed and tested potential inhibitors using our assay and successfully identifying peptidyl α-ketoamide inhibitors of RHBDL4 that are highly effective against recombinant RHBDL4. We utilize ensemble docking and molecular dynamics (MD) simulations to explore the binding modality of substrate-derived peptides bound to RHBDL4. Our analysis focused on key interactions and dynamic movements within RHBDL4's active site that contributed to binding stability, offering valuable insights for optimizing the non-prime side of RHBDL4 ketoamide inhibitors. In summary, our study offers fundamental insights into RHBDL4's catalytic activities and substrate preferences, laying the foundation for downstream applications such as drug inhibitor screenings and structure-function studies, which will enable the identification of lead drug compounds for RHBDL4.

Substrate and Product Selective Supramolecular Catalysis by Pillar[5]arene in the Alkylation of Primary Linear Amines with Allyl Bromide

Substrate and Product Selective Supramolecular Catalysis by Pillar[5]arene in the Alkylation of Primary Linear Amines with Allyl Bromide