Stereochemical antipoles : The myxobacteria Chondromyces crocatus and Myxococcus fulvus utilize tyrosine aminomutase (TAM) enzymes with opposite stereoselectivity to produce β‐Tyr building blocks, which are subsequently incorporated into potent secondary metabolites. The evolution of stereochemical preference within this expanding enzyme family is unexplored. Intriguingly, the mutation of one amino acid in the aminomutase CmdF from C. crocatus influences the enantiomeric excess of (R)‐β‐Tyr formation (see chromatograms).
Enzyme‐mediated synthesis of phosphatidylinositol : Engineered phospholipase D enzymes enable the synthesis of phosphatidylinositol by transphosphatidylation. The 1‐ or 3‐hydroxy group of myo‐inositol is selectively reacted.
A novel design strategy for fluorescent probes based on a pKa switching mechanism was developed. Using this strategy, we developed ratiometric probes for the detection of acid phosphatase activity.
Prodigiosin : Amido‐functionalised prodigiosin‐derived compounds were synthesised via a robust and efficient synthetic route. These compounds were then evaluated against 60 human cell lines consisting of nine diverse tumour cell types and their anticancer activities were assessed.
An inference network model for molecular similarity searching: The similarity search problem is modeled using inference or evidential reasoning under uncertainty. The inference network model treats similarity searching as an evidential reasoning process in which multiple sources of evidence about compounds and reference structures are combined to estimate resemblance probabilities.
Unsaturated Mannich bases with potent antitrypanosomal action against multidrug‐resistant strains of T. brucei brucei were identified. Their observed activities correlated well with their high Michael acceptor properties but not with their affinities to the P2 purine transporter.
Point of recognition : Surface plasmon resonance was used to study the role of the viral membrane in HIV immunogen recognition by the monoclonal antibodies 2F5 and 4E10. The different behaviour of the antibodies towards membranes and immunogens embedded within membranes, provide insight into the emerging membrane‐based or membrane‐conformation strategies of immunogen design.
Reducing virulence : RhlI catalyzes the synthesis of N‐butanoyl homoserine lactone (BHL), with a minor product N‐hexanoyl homoserine lactone (HHL). By using directed evolution and a genetic screen, RhlI has been engineered for enhanced production of both BHL and HHL at a similar level.
Powerful pyrene probes : Two kinds of pyrene‐labeled oligonucleotides (HNA‐ and RNA‐skeleton probes) were explored. The enhanced fluorescence intensity in the monomer region and the disappearance of aggregate/excimer emission in duplexes has been successfully used to detect the hybridization of oligonucleotides.
Particles to the rescue! The construction of cationic amino acid motifs on the surface of bacteriophage Qβ by genetic engineering or chemical conjugation gives particles that are potent inhibitors of the anticoagulant action of heparin, which is a common anticlotting agent subject to clinical overdose.
Natural product libraries for SAR studies : We used a chemical array platform to study the SARs of bleomycin (BLM) derivatives and Shble protein. The on‐chip SARs suggested that several domains are important for recognition of BLMs by Shble protein. In particular, the C‐terminal tail and the propionamide moiety in pyrimidoblamic acid (PBA) were shown to be important for the binding.
Last at last : The terminal step of the gilvocarcin V (GV) biosynthetic pathway is an unusual lactone formation. Here we show that the enzyme, GilR, dehydrogenates the hemiacetal moiety of pregilvocarcin V to the lactone found in GV by using covalently bound FAD.
Choosing chloro : By reshaping the catalytic pocket of a catechol 1,2‐dioxygenase through a structural route alternative to evolution, novel engineered chlorocatechol dioxygenase‐like enzymes were obtained. Variants show an inversion of specificity with a preference for 4‐chlorocatechol and activity on the rarely recognised substrate 4,5‐dichlorocatechol.
The final cut . Two types of artificial tools (artificial restriction DNA cutter and zinc finger nuclease) that cut double‐stranded DNA through hydrolysis of target phosphodiester linkages, have been recently developed. The chemical structures, preparation, properties, and typical applications of these two man‐made tools are reviewed.
Finding the right fit : Herein, we report on the development of novel steric probes and present initial insights into their interplay with DNA polymerases. Our findings provide experimental evidence for varied enzyme–substrate interactions that might account for the varied selectivity previously observed.
In tandem : High‐resolution TEM shows that during the initial stages of demosponge spicule formation, a primordial crystalline structure is formed within the axial filament. The recently developed electron diffraction tomography technique (ADT) reveals that the nanorods have a layered structure that matches smectitic phyllosilicates. These intracellular nanorods have been considered as precursors of mature spicules.
The glycosylation of neuroactive peptides is a promising strategy to treat neurological and psychiatric disorders. Herein we investigated the effects of site‐specific glycosylation of neurotensin (NT). The glycosylated analogues have low‐nanomolar affinities and agonist activities toward NTS1, and suppress seizures with sub‐picomolar potency. Our work points to a new research direction of exploring BBB‐permeable NT analogues as potential first‐in‐class antiepileptic drugs.
Weak recognition processes : Weak calcium‐mediated carbohydrate–carbohydrate interactions have been detected by DOSY and TRNOESY NMR methods by employing a gold glyconanoparticle as a multivalent system. In addition, 3D models of trisaccharide‐CaII‐trisaccharide complexes based on results from molecular dynamics simulations are proposed.
A privileged structure : A library of tetrahydro‐1,4‐pyrazolo‐diazepin‐8(2H)‐ones was designed and synthesized to probe the privileged nature of the scaffold. The design strategy included mimicking the three‐dimensional conformations of β‐turn peptides. Screening against P2X7R, BACE‐1, and MC4R gave several hit compounds for each target. The results suggest that pyrazolodiazepin‐8‐one may represent a potential privileged scaffold.
