It's raining, it's porin : Fragment ligation of OmpF ion channels was achieved by using the split Psp‐GBD Pol intein; this allowed reconstitution of active trimeric porin. In combination with cysteine modification at an internal position, the porin's conductance properties were altered.
Playing polo : Small‐molecule inhibitors of polo‐like kinase 1 are mostly ATP‐competitive, and thus face enormous specificity hurdles. This communication explores the concept of inhibiting Plk1 with a small‐molecule inhibitor of the protein–protein interactions required for Plk1 function.
A series of bicyclic N ‐arylmethyl‐substituted iminoribitols were synthesised and evaluated in vitro against T. vivax nucleoside hydrolase. The importance of the N–Asp40 interaction was confirmed and depends on an optimal pKa value, which can be influenced by substituents. The compounds were active inhibitors of nucleoside hydrolase (IAG‐NH) and are inactive against human purine nucleoside phosphorylase.
Binding of the mGlu2/3 antagonist HYDIA in the closed conformation model of mGlu2 causes repulsive interactions with Y216 in lobe II of the binding pocket, preventing closure of the VFT.
More than the sum of its parts : The seeds of Nigella sativa have been a traditional herbal remedy for ailments such as asthma, diarrhea, and cancer. Their essential oil is rich in polyunsaturated fatty acids and thymoquinone. By linking them covalently, a tremendous boost in anticancer activity can be achieved in resistant tumor cells.
C/Si switch : Twofold sila‐substitution (C/Si exchange) in the RXR‐selective retinoids 4 a (SR11237) and 5 a leads to 4 b (disila‐SR11237) and 5 b , respectively. Chemistry and biology of the C/Si pairs are reported.
The Great White Plague : Mycobacterium tuberculosis, the bacteria causing tuberculosis, is a continuing threat to global health through the emergence of resistant strains and the lack of novel therapeutic agents. Recently reported results on this important work are highlighted.
New geiparvarin derivatives modified at the alkenyloxy bridge, where the 3′‐methyl group was replaced by a hydrogen atom, were synthesized and evaluated against a panel of human tumor cell lines in vitro. Compounds (R)‐ 4 and (R)‐ 5 show greater inhibitory activity toward cell growth than the parent geiparvarin.
Every little drop : The KD values of angiogenin (ANG) interactions as shown by FRET analysis of thousands of pL‐sized droplets agree with data from bulk‐fluorescence polarization measurements. Importantly, the use of fluorophores does not affect the activity of ANG or the binding of anti‐ANG antibodies to ANG. Such an experimental platform could be applied to the high‐throughput analysis of protein–protein interactions.
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.
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.
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).
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.
Asborin , the carbaborane analogue of aspirin, was obtained by a high‐yield synthetic procedure and proved to be an active cyclooxygenase (COX) inhibitor (H: white, B: beige, C: gray, O: blue).
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.
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.
The role of β‐aminovinyl ketones as synthetic intermediates has been well categorised, but recent developments have shown an interesting array of applications and new chemotherapeutic potential, both in the preparation of biologically active heterocycles and as pharmacophores in their own right.
Ancillary oxygenase : OxyE is identified as a likely ancillary C‐4 hydroxylase used during oxytetracycline biosynthesis in Streptomyces rimosus. The synergistic actions of oxygenases OxyE and OxyL ensure complete oxidative tailoring and prevent irreversible shunt modifications of the biosynthetic intermediate.
A QSAR model for the prediction of CNS activity was developed and validated based on data from an in‐house database of “drug‐like” compounds. The model has demonstrated its applicability for novel chemical structures and its usefulness for the design of CNS‐focused compound libraries.
