High Binding Selectivity Research Articles

Development of a Novel Positron Emission Tomography (PET) Radiotracer Targeting Bromodomain and Extra-Terminal Domain (BET) Family Proteins.

Bromodomain and extra-terminal domain (BET) family proteins have become a hot research area because of their close relationship with a variety of human diseases. The non-invasive imaging technique, such as positron emission tomography (PET), provides a powerful tool to visualize and quantify the BET family proteins that accelerating the investigation of this domain. Herein, we describe the development of a promising PET probe, [11C]1, specifically targeting BET family proteins based on the potent BET inhibitor CF53. [11C]1 was successfully radio-synthesized with good yield and high purity after the optimization of radiolabeling conditions. The in vivo bio-activities evaluation of [11C]1 was performed using PET imaging in rodents. The results demonstrated that [11C]1 has favorable uptake in peripheral organs and moderate uptake in the brain. Further blocking studies indicated the high binding specificity and selectivity for BET proteins of this probe. Our findings suggest that [11C]1 is a promising BET PET probe for BET proteins as well as epigenetic imaging.

Nitroxide-Derived N-Oxide Phenazines for Noncovalent Spin-Labeling of DNA.

Two o-benzoquinone derivatives of isoindoline were synthesized for use as building blocks to incorporate isoindoline nitroxides into different compounds and materials. These o-quinones were condensed with a number of o-phenylenediamines to form isoindoline-phenazines in high yields. Subsequent oxidation gave phenazine-di-N-oxide isoindoline nitroxides that were evaluated for noncovalent and site-directed spin-labeling of duplex DNA and RNA that contained abasic sites. Although only minor binding was observed for RNA, the unsubstituted phenazine-N,N-dioxide tetramethyl isoindoline nitroxide showed high binding affinity and selectivity towards abasic sites in duplex DNA that contained cytosine as the orphan base.

Novel peptide ligands for antibody purification provide superior clearance of host cell protein impurities

The quest for ligands alternative to Protein A for the purification of monoclonal antibodies (mAbs) has been pursued for almost three decades. Yet, the IgG-binding peptides known to date still fall short of the host cell protein (HCP) logarithmic removal value (LRV) set by Protein A media (2.5-3.1). In this study, we present an integrated computational-experimental approach leading to the discovery of peptide ligands that provide HCP LRVs on par with Protein A. First, the screening of 60,000 peptide variants was performed using a high-throughput search algorithm to identify sequences that ensure IgG affinity binding. Select sequences WQRHGI, MWRGWQ, RHLGWF, and GWLHQR were then negatively screened in silico against a panel of model HCPs to ensure the selection of peptides with high binding selectivity. Candidate ligands WQRHGI and MWRGWQ were conjugated to chromatographic resins and characterized by isothermal binding and breakthrough assays to quantify static and dynamic binding capacity (Qmax and DBC10%), respectively. The resulting Qmax were 52.6 mg of IgG per mL of adsorbent for WQRHGI and 57.48 mg/mL for MWRGWQ, while the DBC10% (2 minutes residence time) were 30.1 mg/mL for WQRHGI and 36.4 mg/mL for MWRGWQ. Evaluation of the peptides by isothermal titration calorimetry (ITC) confirmed the binding energy predicted in silico, and an amino acid scanning study corroborated the affinity-like binding activity of the peptides. WQRHGI-WorkBeads resin was finally characterized by purification of a monoclonal antibody from a Chinese Hamster Ovary (CHO) cell culture harvest, affording a remarkable HCP LRV of 2.7, and consistent product yield and purity over 100 chromatographic cycles. These results demonstrate the potential of WQRHGI as an effective alternative to Protein A for antibody purification.

Mathematical approaches in estimating aptamer-target binding affinity

The performance of aptamers as versatile tools in numerous analytical applications is critically dependent on their high target binding specificity and selectivity. However, only the technical or methodological aspects of measuring aptamer-target binding affinities are focused, ignoring the equally important mathematical components that play pivotal roles in affinity measurements. In this study, we aim to provide a comprehensive review regarding the utilization of different mathematical models and equations, along with a detailed description of the computational steps involved in mathematically deriving the binding affinity of aptamers against their specific target molecules. Mathematical models ranging from one-site binding to multiple aptameric binding site-based models are explained in detail. Models applied in several different approaches of affinity measurements such as thermodynamics and kinetic analysis, including cooperativity and competitive-assay based mathematical models have been elaborately discussed. Mathematical models incorporating factors that could potentially affect affinity measurements are also further scrutinized.

The selective 5-HT2A receptor agonist 25CN-NBOH: Structure-activity relationship, in vivo pharmacology, and in vitro and ex vivo binding characteristics of [3H]25CN-NBOH

The remarkable effects exhibited by classical psychedelics in recent clinical trials have spawned considerable interest in 5-HT2A receptor (5-HT2AR) activation as a treatment strategy for several psychiatric/cognitive disorders. In this study we have continued our development of 25CN-NBOH, one of the most 5-HT2AR-selective agonists reported to date, as a pharmacological tool for exploration of 5-HT2AR expression and functions. The importance of the 2′ and 3′ positions in 25CN-NBOH as structural hotspots for its 5-HT2AR activity was investigated by synthesis and pharmacological characterization of six novel analogs at 5-HT2AR and 5-HT2CR in binding and functional assays. While the 5-HT2AR activity of 25CN-NBOH was retained in 3′-methyl, 2′,3′-chroman, 2′,3′-dihydrofuran and 2′,3′-furan analogs, the 3′-methoxy and 3′-ethyl analogs displayed substantially lower binding affinities and agonist potencies than 25CN-NBOH. Interestingly, the 2′,3′-substitution pattern was also a key determinant of agonist efficacy, as all six analogs exhibited low-efficacy partial agonism or de facto antagonism at the 5-HT2AR in the functional assays. Systemic administration of 25CN-NBOH and its close structural analog 25CN-NBMD induced robust head-twitch response in mice, a well-established behavioural effect of 5-HT2AR activation in vivo, and 25CN-NBOH mediated robust reductions in the activity of mice in an anxiety-related marble burying assay, which supports the proposed beneficial effects of 5-HT2AR activation on disorders characterized by cognitive rigidity. Finally, tritiated 25CN-NBOH exhibited high 5-HT2AR binding affinity (KD ~1 nM) and selectivity against 5-HT2BR and 5-HT2CR in equilibrium and kinetic binding studies of the recombinant receptors, and in concordance [3H]25CN-NBOH displayed substantial specific, ketanserin-sensitive binding to cortex and small levels of binding to choroid plexus in rat brain slices in autoradiography studies. In conclusion, this work delineates the subtle molecular determinants of the 5-HT2AR activity in 25CN-NBOH, substantiates the potential in this compound and its analogs as tools for in vivo studies of the 5-HT2AR, and introduces a novel selective agonist radioligand as another potentially valuable tool for future explorations of this receptor.

Redox-Responsive Host-Guest Chemistry of a Flexible Cage with Naphthalene Walls.

"Naphthocage", a naphthalene-based organic cage, reveals very strong binding (up to 1010 M-1) to aromatic (di)cationic guests, i.e., the tetrathiafulvalene mono- and dication and methyl viologen. Intercalation of the guests between two naphthalene walls is mediated by C-H···O, C-H···π, and cation···π interactions. The guests can be switched into and out of the cage by redox processes with high binding selectivity. Oxidation of the flexible cage itself in the absence of a guest leads to a stable radical cation with the oxidized naphthalene intercalated between and stabilized by the other two. Encapsulated guest cations are released from the cavity upon cage oxidation, paving the way to future applications in redox-controlled guest release or novel stimuli-responsive materials.

Benzenebistriazole-strapped calix[4]pyrrole: a neutral anion receptor with CH and NH donor groups that exhibits high sulfate binding affinity and selectivity in aqueous solutions.

A calix[4]pyrrole strapped by benzenebistriazole has been prepared as an artificial anion binding receptor. This neutral anion receptor shows high sulfate binding affinity and selectivity in an aqueous solution. In solid state, the receptor binds the sulfate anion in a chair-like 3D cavity via multiple N-H and C-H hydrogen bonds.

Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells.

IntroductionCancer gene therapy requires both effective tumor suppressor genes and safe vectors that express target genes efficiently. Inhibitor of growth 4 (ING4) inhibits tumor growth via multiple pathways. Interleukin-24 (IL-24) also has tumor-suppressive activity against a broad spectrum of human cancers. Adenovirus (Ad) vectors exhibit high infection efficiency, but potential toxicity related to high doses of adenovirus has led to careful reconsideration of their use in human clinical trials. Antheraea pernyi silk fibroin (ASF) is a cytocompatible and biodegradable natural polymer, and it possesses Arg–Gly–Asp sequences exhibiting a high binding affinity and selectivity for αvβ3 and αvβ5 integrin receptors, which are overexpressed in tumor vessels and most tumor cells.MethodsIn this study, an Arg-Gly-Asp peptide-modified Ad vector coexpressing ING4 and IL-24 was constructed by homologous recombination of the dual gene coexpression transfer plasmid and RGD-modified pAdEasy-1 adenoviral backbone plasmid. The cationic ASF (CASF) was prepared by modifying ASF with low-molecular-weight PEI. The negatively charged Ad vector was modified with CASF to form a CASF/Ad complex.ResultsHuman hepatoma carcinoma SMMC-7721 cells and normal hepatic L-02 cells were infected with the CASF/Ad complex, which showed significantly higher infection efficiency than the naked Ad. The CASF/Ad complex could effectively mediate the expression of the target gene ING4 in SMMC-7721 cells and the secretion of the target gene IL-24 from SMMC-7721 cells, thus inducing apoptosis of hepatoma carcinoma SMMC-7721 cells. The viability of SMMC-7721 and L-02 cells infected with the CASF/Ad complex was further assessed, and it was found that the growth of SMMC-7721 cells was significantly inhibited but that the growth and proliferation of L-02 cells were not affected.ConclusionThe CASF/Ad complex constructed in this study, showing improved infection efficiency and enhanced suppressive effects on human hepatoma carcinoma SMMC-7721 cells, has the potential to reduce the dose of adenovirus and still maintain high infection efficiency and tumor inhibition.

Selective binding of antibiotics using magnetic molecular imprint polymer (MMIP) networks prepared from vinyl-functionalized magnetic nanoparticles

Adverse effects of pharmaceutical emerging contaminants (PECs), including antibiotics, in water supplies has been a global concern in recent years as they threaten fresh water security and lead to serious health problems to human, wildlife and the environment. However, detection of these contaminants in water sources, as well as food products, is difficult due to their low concentration. Here, we prepared a new family of magnetic molecular imprinted polymer (MMIP) networks for binding antibiotics via a microemulsion polymerization technique using vinyl silane modified Fe3O4 magnetic nanoparticles. The cross-linked polymer backbone successfully integrated with 20−30 nm magnetic nanoparticles and generated a novel porous polymeric network structure. These networks showed a high binding capacity for both templates, erythromycin and ciprofloxacin at 70 and 32 mg/g. Both MMIPs were also recyclable, retaining 75 % and 68 % of the binding capacity after 4 cycles. These MMIPs have showed a clear preference for binding the template molecules, with a binding capacity 4- to 7-fold higher than the other antibiotics in the same matrix. These results demonstrate our MMIP networks, which offered high binding capacity and selectivity as well as recyclability, can be used for both removal and monitoring hazardous antibiotic pollutants in different sources/samples and food products.

A dual-step immobilization/imprinting approach to prepare magnetic molecular imprinted polymers for selective removal of human serum albumin

One viable solution to improve the conformational stability of template proteins is to use multiple, weaker modes of action to immobilize proteins on the surfaces of a solid support. Herein, we introduce a novel surface imprinting technique for human serum albumin (HSA) by a dual immobilization/imprinting strategy. Specifically, HSA was first conjugated to the surfaces of magnetic Fe3O4 nanoparticles through a reversible aldmine condensation reaction. Dopamine (DA) was then used to imprint the protein template via an auto-polymerization reaction in biocompatible aqueous media. The resultant magnetic molecular imprinted polymers (MMIPs) possess high adsorption capacity (70.2 mg g−1), superior selectivity (IF = 4.54), and rapid capturing kinetics to HSA (within 20 min). We successfully demonstrate the practical applicability of MMIPs to the selective removal of HSA from human serum sample. Our work offers a novel and robust solution to develop proteins imprinted materials with high binding capacity and selectivity. We anticipate such materials will find wide applications to protein detection or removal in diverse real-life clinical and biological samples.

Systematic search for structural motifs of peptide binding to double-stranded DNA.

A large variety of short biologically active peptides possesses antioxidant, antibacterial, antitumour, anti-ageing and anti-inflammatory activity, involved in the regulation of neuro-immuno-endocrine system functions, cell apoptosis, proliferation and differentiation. Therefore, the mechanisms of their biological activity are attracting increasing attention not only in modern molecular biology, biochemistry and biophysics, but also in pharmacology and medicine. In this work, we systematically analysed the ability of dipeptides (all possible combinations of the 20 standard amino acids) to bind all possible combinations of tetra-nucleotides in the central part of dsDNA in the classic B-form using molecular docking and molecular dynamics. The vast majority of the dipeptides were found to be unable to bind dsDNA. However, we were able to identify 57 low-energy dipeptide complexes with peptide-dsDNA possessing high selectivity for DNA binding. The analysis of the dsDNA complexes with dipeptides with free and blocked N- and C-terminus showed that selective peptide binding to dsDNA can increase dramatically with the peptide length.

Identification and evaluation of glutathione conjugate gamma-l-glutamyl-l-cysteine for improved drug delivery to the brain

Glutathione (GU), an endogenous antioxidant tripeptide, is frequently transferred in the human brain through N-methyl-d-aspartate receptor (NMDAR), profusely expressed at the blood–brain barrier (BBB) junction. GU, also modifies the characteristics of tight junction proteins (occludin and claudin) at the site of BBB by depolarizing the enzyme, protein tyrosine phosphatase that manifests its usefulness for passive delivery of nanocarriers to the brain. GU, thus, represents itself as an ideal ligand for the surface decoration of nanocarriers to successfully administer them across the brain via receptor-mediated drug delivery pathway. Hence, we have employed here, in-silico approaches to identify the potential GU-like molecules, as appropriate ligand(s) for surface engineering of nanoconstruct with the purpose of attaining targeted drug delivery to the brain. Structure-based virtual screening methods was used to filter PubChem database for the identification of bioactive compounds with >95% structure similarity with GU. We have further screened the compounds against NMDAR using molecular docking approach. Top hits were selected based on their high binding affinities and selectivity towards NMDAR, and their binding pattern was analysed in detail. Finally, all atom molecular dynamics simulation for 100 ns was carried out on free NMDAR and in-presence of the selected GU-like compound, gamma-l-glutamyl-l-cysteine to evaluate complex stability and structural dynamics. In conclusion, gamma-l-glutamyl-l-cysteine may act as potential binding partner of NMDAR which can further be evaluated in drug delivery system to brain across the BBB.Communicated by Ramaswamy H. Sarma

Bioprospecting solid binding polypeptides for lithium ion battery cathode materials.

Biotemplating presents a promising approach to improve the performance of inorganic materials via specific control over morphology, crystal structure, and the size of particles during synthesis and assembly. Among other biotemplates, solid binding polypeptides (SBPs) isolated for the material of interest provide high binding affinity and selectivity due to distinct combinations of functional groups found in amino acids. Nanomaterials assembled and synthesized with SBPs have found widespread applications from drug delivery to catalysis and energy storage due to their improved properties. In this study, the authors describe the identification of SBPs for binding to Li-ion battery cathode materials LiCoPO4, LiMn1.5Ni0.5O4, and LiMn2O4, which all have potential for improvement toward their theoretical values. The binding affinity of isolated peptides was assessed via phage binding assays and confirmed with electron microscopy in order to select for potential biotemplates. The authors demonstrate ten binding peptides for each material and analyze the sequences for enrichment in specific amino acids toward each structure (olivine and spinel oxide), as well as the test for specificity of selected sequences. In further studies, the authors believe that the isolated SBPs will serve as a template for synthesis and aid in assembly of cathode materials resulting in improved electrochemical properties for Li-ion batteries.

A new tetrapeptide biomimetic chromatographic resin for antibody separation with high adsorption capacity and selectivity

Biomimetic affinity chromatography with short peptide ligands is a developing technology, which has great potential for antibody separation and purification. In this study, a tetrapeptide library with critical residues of natural ligands to hIgG was constructed and a novel tetrapeptide ligand (Ac-FYHE) with high LibDock scores was selected by molecular docking. Then, Ac-FYHE ligand was linked to agarose bead to prepare a new chromatography resin. The properties of antibody adsorption were measured and evaluated by static/dynamic adsorption. It was found that the resin with ligand Ac-FYHE has high binding capacity and selectivity for hIgG. The results showed the Qm-hIgG of Ac-FYHE-4FF resin was 87.9 mg/g resin while the Qm-BSA of this resin was only 16.5 mg/g resin at pH 7.0. Moreover, at pH 7.0, Q10% of Ac-FYHE-4FF resin was 24.1 mg/mL for hIgG but just 2.1 mg/mL for BSA, which presented high selectivity of the screened resin at pH 7.0. Subsequently, the adsorption and separation properties of the Ac-FYHE-4FF resin were further investigated. As a result, with the addition of 0.5 M NaCl, Qm decreased by less than 20% but Qm decreased by 70% with the addition of 50% (v/v) ethylene glycol, which indicated that hydrophobic interaction would be the driving force for the binding between resin and hIgG. Besides, pH 7.5 and pH 4.5 could be the optimal loading and elution condition for hIgG, respectively. Finally, the Ac-FYHE-4FF resin was applied to separate mAb or/and hIgG from BSA containing feedstock, CHO cell culture supernatant and human serum, and the purity and recovery were both more than 90% with only one-step separation. The results indicate that the Ac-FYHE-4FF resin developed in this work would be promising for antibody separation and purification.

Chromatin accessibility plays a key role in selective targeting of Hox proteins

BackgroundHox transcription factors specify segmental diversity along the anterior-posterior body axis in metazoans. While the different Hox family members show clear functional specificity in vivo, they all show similar binding specificity in vitro and a satisfactory understanding of in vivo Hox target selectivity is still lacking.ResultsUsing transient transfection in Kc167 cells, we systematically analyze the binding of all eight Drosophila Hox proteins. We find that Hox proteins show considerable binding selectivity in vivo even in the absence of canonical Hox cofactors Extradenticle and Homothorax. Hox binding selectivity is strongly associated with chromatin accessibility, being highest in less accessible chromatin. Individual Hox proteins exhibit different propensities to bind less accessible chromatin, and high binding selectivity is associated with high-affinity binding regions, leading to a model where Hox proteins derive binding selectivity through affinity-based competition with nucleosomes. Extradenticle/Homothorax cofactors generally facilitate Hox binding, promoting binding to regions in less accessible chromatin but with little effect on the overall selectivity of Hox targeting. These cofactors collaborate with Hox proteins in opening chromatin, in contrast to the pioneer factor, Glial cells missing, which facilitates Hox binding by independently generating accessible chromatin regions.ConclusionsThese studies indicate that chromatin accessibility plays a key role in Hox selectivity. We propose that relative chromatin accessibility provides a basis for subtle differences in binding specificity and affinity to generate significantly different sets of in vivo genomic targets for different Hox proteins.

Highly stable hexitol based XNA aptamers targeting the vascular endothelial growth factor.

Biomedical applications of nucleic acid aptamers are limited by their rapid degradation in biological fluids and generally demand tedious post-selection modifications that might compromise binding. One possible solution to warrant biostability is to directly evolve chemically modified aptamers from xenobiotic nucleic acids (XNAs). We have isolated fully modified 2′-O-methyl-ribose–1,5-anhydrohexitol nucleic acid (MeORNA–HNA) aptamers targeting the rat vascular endothelial growth factor 164 (rVEGF164). Three sequences have been identified that interact with the target protein with affinities in the low-nanomolar range and HNA modifications appeared to be mandatory for their tight binding. The evolution of these XNA aptamers was accomplished using an in vitro selection procedure starting from a fully sugar-modified library containing a 20mer 2′-OMe-ribonucleotide region followed by a 47mer HNA sequence. The high binding affinity and selectivity of the selected aptamers were confirmed by several methods including gel-shift, fluorescence polarisation, and enzyme-linked oligonucleotide assays. The isolated HNA ligands exhibited higher specificity to the rVEGF164 and human VEGF165 isoforms compared to rat VEGF120, while very low binding efficiencies were observed to streptavidin and thrombin. Furthermore, it was clearly demonstrated that the resulting aptamers possessed a superior stability to degradation in human serum and DNase I solutions.

Identification of novel imidazole flavonoids as potent and selective inhibitors of protein tyrosine phosphatase

A series of imidazole flavonoids as new type of protein tyrosine phosphatase inhibitors were synthesized and characterized. Most of them gave potent protein phosphatase 1B (PTP1B) inhibitory activities. Especially, compound 11a could effectively inhibit PTP1B with an IC50 value of 0.63 μM accompanied with high selectivity ratio (9.5-fold) over T-cell protein tyrosine phosphatase (TCPTP). This compound is cell permeable with relatively low cytotoxicity. The high binding affinity and selectivity was disclosed by molecular modeling and dynamics studies. The structural features essential for activity were confirmed by quantum chemical studies.

A fluorescence-displacement assay using molecularly imprinted polymers for the visual, rapid, and sensitive detection of the algal metabolites, geosmin and 2-methylisoborneol

A visual, rapid, and sensitive method for the detection of two algal metabolites, geosmin (GSM) and 2-methylisoborneol (2-MIB) using a competitive displacement technique based on molecular imprinted polymers (MIPs) and fluorescent tags was developed. In this method, fluorescent tags that bind to synthetic receptor sites of MIPs were designed and synthesised. In the presence of target analytes (geosmin and 2-methylisoborneol respectively), the tags are displaced leading to fluorescence signals. The MIPs were derived from the polymerisation of functional monomers and crosslinkers in the presence of suitable templates. Good to high binding capacities and selectivities were obtained with the MIPs. The displacement of fluorescent-tagged substrates from the respective MIPs by the target analytes enabled the quantitative detection of geosmin at concentrations as low as 0.38 μM (69 μg L−1), while the LOD for 2-methylisoborneol is 0.29 μM (48 μg L−1) without any cross-reactivity, non-specific (false-positive) binding, and matrix complications. Qualitative detection of geosmin and 2-methylisoborneol is also possible via visualisation of fluorescence using a hand held UV lamp, with LOD for geosmin and 2-methylisoborneol at 0.44 μM (80 μg L−1) and 0.35 μM (60 μg L−1), respectively. The sensitivity of the system can be improved with a pre-concentration step using the respective MIPs as a sorbent.

Katrina (Kate) Jolliffe

Angewandte Chemie International EditionVolume 58, Issue 10 p. 2939-2939 Author ProfileFree Access Katrina (Kate) Jolliffe First published: 18 January 2019 https://doi.org/10.1002/anie.201814455AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract “When I was eighteen I wanted to be a chef. My favorite musicians are Nick Cave and PJ Harvey …” Find out more about Katrina A. Jolliffe in her Author Profile. Katrina (Kate) Jolliffe Katrina A. Jolliffe was recently honored with the RACI H. G. Smith Memorial Award. Her most recent contribution to Angewandte Chemie is published in this issue: “A Fluorogenic Probe for Cell Surface Phosphatidylserine Using an Intramolecular Indicator Displacement Sensing Mechanism”: V. E. Zwicker, B. L. Oliveira, J. H. Yeo, S. T. Fraser, G. J. L. Bernardes, E. J. New, K. A. Jolliffe, Angew. Chem. Int. Ed. 2019, 58, 3087; Angew. Chem. 2019, 131, 3119. Date of birth: April 10, 1970 Position: Professor of Chemistry, The University of Sydney E-mail: kate.jolliffe@sydney.edu.au Homepage: http://sydney.edu.au/science/people/kate.jolliffe.php ORCID: 0000-0003-1100-4544 Education: 1992 BSc, University of New South Wales (NSW) 1996 PhD (supervised by Prof. Michael Paddon-Row), University of NSW 1996–1998 Postdoctoral fellow with Prof. David Reinhoudt, Twente Universiteit 1998–2000 Postdoctoral fellow with Prof. Gerald Pattenden, University of Nottingham 2000–2002 Postdoctoral fellow with Prof. Martin G. Banwell, Australian National University Awards: 2004 Beckwith Lectureship for Organic Chemistry (Royal Australian Chemical Institute; RACI); 2006 Biota Award for Medicinal Chemistry (RACI); 2007 Young Tall Poppy Science Award; 2017 A. J. Birch Medal (RACI); 2018 H. G. Smith Memorial Award Research: Anion recognition, self-assembly, hydrogen bonding, cyclic peptides Hobbies: Cooking (and eating good food!), gardening, reading fiction When I was eighteen I wanted to be a chef—but synthetic chemistry can sometimes be a lot like cooking so that worked out. My favorite musicians are Nick Cave and PJ Harvey—I can't choose between them. I am waiting for the day when someone will discover a good cloning method, so one of me can be at work while the other one is on the beach. Of course, we'd need to be able to sync our clone minds so the beach me didn't get bored and the work me didn't get too stressed. Last time I went to the pub I was celebrating acceptance of my Angewandte Chemie manuscript on phosphatidylserine sensing. My favorite drink is gin, no need for tonic. My first experiment was in primary school. I tried to measure how things appear to increase in size when viewed through a drop of water. If I could be any age I would be my current age, but would have spent more time at the gym when I was younger! I advise my students to gain good time management skills and work smarter not longer hours. My favorite way to spend a holiday is reading a novel on a sunny beach. Preferably the beach is in Spain so I can go out for tapas afterwards. The most important thing I learned from my students is that most of them are smarter than me. What I appreciate most about my friends is their ability to make me laugh and forget about work for a while. My 5 top papers: 1“Macrocyclic squaramides: anion receptors with high sulfate binding affinity and selectivity in aqueous media”: L. Qin, A. Hartley, P. Turner, R. B. P. Elmes, K. A. Jolliffe, Chem. Sci. 2016, 7, 4563. (Anion-binding macrocycles that are able to discriminate sulfate from chromate with better selectivity than the sulfate-binding protein.) 2“Janus Cyclic Peptide—Polymer Nanotubes”: M. Danial, C. M.-N. Tran, P. G. Young, S. Perrier, K. A. Jolliffe, Nature Commun. 2013, 2780. (Self-assembled polymer-coated cyclic peptide nanotubes that cluster together to poke holes in membranes.) 3“Selective Pyrophosphate Recognition by Cyclic Peptide Receptors in Physiological Saline”: S. J. Butler, K. A. Jolliffe, Chem. Asian J. 2012, 7, 2621. (Counterintuitively, binding selectivity by chemosensing ensembles can be improved in more complex environments.) 4“Pseudo-prolines as Removable Turn Inducers: Tools for the Cyclisation of Small Peptides”: D. Skropeta, K. A. Jolliffe, P. Turner, J. Org. Chem. 2004, 69, 8804. (My first publication as an independent researcher, describing a useful methodology for the improved synthesis of head-to-tail cyclic peptides.) 5“Noncovalent Assembly of a Fifteen-Component Hydrogen-Bonded Nanostructure”: K. A. Jolliffe, P. Timmerman, D. N. Reinhoudt, Angew. Chem. Int. Ed. 1999, 38, 933; Angew. Chem. 1999, 111, 983. (My first foray into this exciting area of chemistry.) Volume58, Issue10Special Issue: Women in ChemistryMarch 4, 2019Pages 2939-2939 ReferencesRelatedInformation

Carboxylated pillar[n]arene (n = 5-7) host molecules: high affinity and selective binding in water.

Water-soluble carboxylated pillar[n]arenes (n = 5-7) or WPns were discovered to be high affinity host molecules with selective binding for different guests based on a systematic investigation. We chose 22 dyes or guests and determined the value of Ka for 51 supramolecular complexes. It was discovered that the electrostatic interactions, π-π stacking and hydrophobic effect were the driving force for high affinity supramolecular encapsulation. WPns had selective binding toward suitable guests based on their sizes and molecular structures. Based on the above discovery, a guest (guest 21) was designed, which bound with WP7 3.3-fold tighter compared to methyl viologen.