Safety-catch linker strategies for the production of radiopharmaceuticals labeled with positron-emitting isotopes

A novel synthetic stratetegy for compounds labeled with the positron-emitting isotope carbon-11 is described. The use of precursors attached to a solid support via safety-catch linkers allows selective release of radiolabeled material, leaving unreacted precursor attached to the support. Two different linkers demonstrate the application to the preparation of radiolabeled N-alkyl tertiary amines and N-alkylsulfonamides. This technique is expected to lead to more widespread use of positron emission tomography for the in vivo analysis of compound behavior.     

Ultrasonic density measurement for process control

A method has been devised for determining the density of a fluid by measuring the velocity and amplitude of an ultrasonic pulse passed through it. The theory of the method is presented, together with the results of an experimental verification.     

Enantiospecific formal total synthesis of the tumor and GSK-3 beta inhibiting alkaloid, (-)-agelastatin A

[reaction: see text] An enantiospecific total synthesis of Weinreb's advanced intermediate 2 for (-)-agelastatin A has been achieved from the Hough-Richardson aziridine 8. Noteworthy reactions in our sequence include the highly regioselective trans-diaxial ring-opening of 8 with azide ion to set up the vicinal diamido functionality present within (-)-2 and the Grubbs-Hoveyda ring-closing metathesis (RCM) reaction that was used to construct its cyclopentene core.     

Asymmetric synthesis of the C(1)C(47) backbone of antitumour antibiotic A83586C

Protected pentapeptide 9 has been converted to hexapeptide 3 and this chemoselectively coupled to activated ester 2 to give 1 after glycal hydration during SiO₂ flash chromatography.     

A Quantitative Tool to Distinguish Isobaric Leucine and Isoleucine Residues for Mass Spectrometry-Based De Novo Monoclonal Antibody Sequencing

De novo sequencing by mass spectrometry (MS) allows for the determination of the complete amino acid (AA) sequence of a given protein based on the mass difference of detected ions from MS/MS fragmentation spectra. The technique relies on obtaining specific masses that can be attributed to characteristic theoretical masses of AAs. A major limitation of de novo sequencing by MS is the inability to distinguish between the isobaric residues leucine (Leu) and isoleucine (Ile). Incorrect identification of Ile as Leu or vice versa often results in loss of activity in recombinant antibodies. This functional ambiguity is commonly resolved with costly and time-consuming AA mutation and peptide sequencing experiments. Here, we describe a set of orthogonal biochemical protocols, which experimentally determine the identity of Ile or Leu residues in monoclonal antibodies (mAb) based on the selectivity that leucine aminopeptidase shows for n-terminal Leu residues and the cleavage preference for Leu by chymotrypsin. The resulting observations are combined with germline frequencies and incorporated into a logistic regression model, called Predictor for Xle Sites (PXleS) to provide a statistical likelihood for the identity of Leu at an ambiguous site. We demonstrate that PXleS can generate a probability for an Xle site in mAbs with 96% accuracy. The implementation of PXleS precludes the expression of several possible sequences and, therefore, reduces the overall time and resources required to go from spectra generation to a biologically active sequence for a mAb when an Ile or Leu residue is in question.

Unusual Electro‐Optic Kerr Response in a Self‐Stabilized Amorphous Blue Phase with Nanoscale Smectic Clusters

We investigated the electro‐optic response in the “foggy” amorphous blue phase (BPIII) as well as in the isotropic phase. To the best of our knowledge, such a study has not yet been performed due to the very limited thermal range of BPIII. In this study, we used a single‐component chiral bent‐core liquid crystal with a self‐stabilized BPIII, which is stable over a wide temperature range. The results show that the response time is on the order of hundreds of microseconds in the isotropic phase and increases to 1–2 ms in the BPIII (at T_I?BP–T <1), then drastically increases up to a few tens of milliseconds upon further cooling in BPIII. Such an unusual behavior was explained on the basis of the high rotational viscosity and/or the existence of nanoscale smectic (Sm) clusters. The Kerr constant was also measured and found to be ～500 pm V^?2, which is the largest among bent‐core BP systems reported so far and comparable with that of polymer‐stabilized BPs.     

Amperometric glycolate sensors based on glycolate oxidase and polymeric electron transfer mediators

Using experiments involving cyclic voltammetry and stationary potential measurements, it was shown that siloxane polymers with covalently attached ferrocene and 1,1'-dimethylferrocene relays efficiently mediate electron transfer from reduced glycolate oxidase to a conventional carbon-paste electrode. Sensors containing these polymeric relay systems and glycolate oxidase respond rapidly to low (< 0.1 mM) glycolate concentrations, with steady-state current responses achieved in less than 1 min. The dependence of the sensor response on the nature of the siloxane polymer backbone, the type of polymer-bound redox mediator used and the amount of redox mediator present is discussed. From these considerations, sensors have been designed which can operate efficiently at low applied potential and can avoid decreased current response due to dissolved oxygen.