Reversible 5′-end biotinylation and affinity purification of synthetic RNA

A reversible biotinylation phosphoramidite was synthesized and incorporated onto the 5′-end of an oligoribonucleotide on a solid phase synthesizer. After cleavage and deprotection, the crude synthetic oligomer mixture was incubated with NeutrAvidin^® coated microspheres, and the failure sequences removed by washing with a buffer followed by treating the microspheres with tetrabutylammonium fluoride to give a high quality unmodified full-length oligoribonucleotide.     

Ligand creation via linking—a rapid and convenient method for construction of novel supported PyOX-ligands

A novel supported amino alcohol linker was synthesized and utilized for attachment of picolinic acid derivatives onto different supports. When the resin bound molecule was further activated, the PyOX-moiety could be constructed reliably in enantiopure form. Furthermore, an efficient Pd-catalyzed modification of a picolinic acid derivative is presented.     

Application of Cleavable Linkers to Improve Therapeutic Index of Radioligand Therapies

Radioligand therapy (RLT) is an emergent drug class for cancer treatment. The dose administered to cancer patients is constrained by the radiation exposure to normal tissues to maintain an appropriate therapeutic index. When a radiopharmaceutical or its radiometabolite is retained in the kidneys, radiation dose deposition in the kidneys can become a dose-limiting factor. A good exemplar is [¹⁷⁷Lu]Lu-DOTATATE, where patients receive a co-infusion of basic amino acids for nephroprotection. Besides peptides, there are other classes of targeting vectors like antibody fragments, antibody mimetics, peptidomimetics, and small molecules that clear through the renal pathway. In this review, we will review established and emerging strategies that can be used to mitigate radiation-induced nephrotoxicity, with a focus on the development and incorporation of cleavable linkers for radiopharmaceutical designs. Finally, we offer our perspectives on cleavable linkers for RLT, highlighting future areas of research that will help advance the technology.     

Recycling solid supports – A head-to-tail linker

The concept of a `head-to-tail linker' designed to allow the regeneration and reuse of a variety of solid supports is introduced. The synthesis of this linker, its coupling to various solid supports, its application in a number of standard solid phase reactions and resin regeneration are presented.     

Nucleoside and oligonucleotide pyrene conjugates with 1,2,3-triazolyl or ethynyl linkers: synthesis,duplex stability,and fluorescence changes generated by the DNA-dye connector

Fluorescent nucleosides and oligonucleotides functionalized with pyrene were synthesized using ‘click’ chemistry or the Sonogashira cross-coupling reaction. The dye was connected to position-7 of 7-deaza-2′-deoxyguanosine or to the 2′-deoxyribofuranose moiety. Four different DNA-dye connectors with 1,2,3-triazolyl residues or triple bonds were constructed. Phosphoramidites of the pyrene conjugates (9, 14, 25) were prepared and used in solid-phase synthesis. Short linkers (2, 4) destabilize DNA, while long linkers (1) increased duplex stability. Nucleosides and oligonucleotides with single dye incorporations show linker dependent fluorescence. Linker dependent excimer emission with pyrenes in proximal positions was also observed. A ‘superchromophore’ formed by the 7-deaza-2′-deoxyguanosine ethynylpyrene conjugate shows strong red shifted fluorescence emission at 495 nm.     

Synthetic methods for polyamine linkers and their application to combinatorial chemistry

Summary Polyamines and polyamine conjugates display a diverse range of important biological functions, ranging from antibiotics to immunosuppressants and glutamate receptor antagonists. For these reasons, polyamines provide an excellent template/scaffold for combinatorial chemistry. In this paper we present methods for the solid-phase immobilisation of polyamines for use in synthetic and combinatorial chemistry and describe how they have been employed in the preparation of a number of important polyamine conjugates and polyamine libraries. Thus, we have designed, synthesised and utilised a number of polyamine linkers for both solution and resin screening combinatorial application.     

Highly efficient water‐soluble visible light photoinitiators

The monoacylphosphineoxide (MAPO) salts Na‐TPO and Li‐TPO and the bisacylphosphineoxide (BAPO) salts BAPO‐ONa and BAPO‐OLi define an important and in the latter case a new class of water‐soluble photoinitiators (PIs) for radical polymerization. These compounds showed excellent water‐solubility of at least 29 g/L for Na‐TPO and up to 60 g/L for BAPO‐ONa in deionized water, thus exceeding the solubility of the state of the art PI for water‐based systems Irgacure 2959 ( I2959 ) 6‐ to 12‐fold. However, biocompatibility, storage stability, and reactivity were equally important to replace the state of the art compounds. Concerning these properties, the MAPO and BAPO salts were at least in the same range (biocompatibility, stability) or showed even better results (reactivity) and had the additional advantage of visible light initiation. Na‐TPO and Li‐TPO achieved double bond conversions of an aqueous solution of N‐acryloylmorpholine over 97% with broad band irradiation (320–500 nm), Li‐TPO showed additionally very good biocompatibility (LC₅₀ = 3.1 mmol/L) and BAPO‐OLi showed highest reactivity with visible light irradiation. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 473–479     

A straightforward preparation of amino–polystyrene resin from Merrifield resin

Azidomethyl–polystyrene, obtained by nucleophilic substitution of chloromethyl–polystyrene, undergoes a Schmidt rearrangement when treated with trifluoromethanesulfonic acid, affording amino–polystyrene. To assess its loading and reactivity the resin is used as a support for the preparation of triazene-linked amine.     

Optimization of spiroimidazolidinone derivatives synthesis on solid phase using SynPhase™ Lanterns

We report the synthesis of 1,4,8-triazaspiro[4.5]decan-2-one derivatives from N-benzyl-4-piperidone and N-protected amino acid amides on solid support. We have translated the chemistry from solution to solid phase using a backbone amide linker (BAL) mimic. Using a parallel combinatorial approach, we performed the optimization of the synthesis on SynPhase™ Lanterns.     

Hybrid cross‐linked hydrogels as a technology platform for in vitro release of cephradine

Hydrogel‐based drug delivery systems can leverage therapeutically favorable upshots of drug release and found clinical uses. Hydrogels offer temporal and spatial control over the release of different therapeutic agents. Because of their tailor made controllable degradability, physical properties, and ability to prevent the labile drugs from degradation, hydrogels provide platform on which diverse physicochemical interactions with entrapped drugs cause to control drug release. Herein, we report the fabrication of novel vinyltrimethoxy silane (VTMS) cross‐linked chitosan/polyvinyl pyrrolidone hydrogels. Swelling in distilled water in conjunction with different buffer and electrolyte solutions was performed to assess the swellability of hydrogels. Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X‐ray diffraction (XRD) analysis were further conducted to investigate the possible interactions between components, thermal stability, and crystallinity of as‐prepared hybrid hydrogels, respectively. In vitro time‐dependent biodegradability, antimicrobial study, and cytotoxicity were also carried out to evaluate their extensive biocompatibility and cytotoxic behavior. More interestingly, in vitro drug release study allowed for the controlled release of cephradine. Therefore, this facile strategy developed the novel biocompatible and biodegradable hybrid hydrogels, which could significantly expand the scope of these hydrogels in other biomedical applications like scaffolds, skin regeneration, tissue engineering, etc.