Provided herein are processes for preparing an oligomer (e.g., a morpholino oligomer). The synthetic processes described herein may be advantageous to scaling up oligomer synthesis while maintaining overall yield and purity of a synthesized oligomer.

Protected fluorescent reagent compounds and their methods of synthesis are provided. The compounds are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The compounds contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements.

Compounds of formula (I):

##STR00001##

wherein Het, R.sub.3, R.sub.4, R.sub.5, R.sub.7, R.sub.8, R.sub.9, T, p, p′, q, and q′ are as defined in the description.

Medicinal products containing the same which are useful in treating conditions requiring a pro-apoptotic agent.

The disclosure relates to nucleic acids that contain modifications at the 5′-end, 3′-end or 5′-end and 3′-ends, and compounds that can be used to make the modified nucleic acids arc disclosed. The modified nucleic acids have improved expression, lower immunogenicity and improved stability compared to unmodified nucleic acids.

Methods of treating neurological inflammatory disease or seizures caused by neuroinflammation by administering cPMP are described. Treating neuroinflammatory and neurometabolic diseases with cPMP is described so as to override dyshomeostasis in the MoCo synthesis pathway and control synaptic inhibition in the gephyrin-GABAR pathway. This is a novel strategy for preventing neural circuit dyshomeostasis by stabilizing inhibitory synapses.

The present invention relates to an oligonucleotide comprising at least one phosphorodithioate internucleoside linkage of formula (I) (I) as defined in the description and in the claim. The oligonucleotide of the invention can be used as a medicement.

##STR00001##

A method for subjecting a compound [A] having a hydroxyl group or a primary or secondary amino group and a compound [B] having a substituent containing a phosphorus atom to a condensation reaction to prepare a compound [C] represented by the following general formula [C]: ##STR00001##
wherein the condensation reaction is carried out in a mixed solvent containing a polar solvent and a halogen solvent as a reaction solvent.

The present invention relates to a method for producing a compound [C] of the general formula [C] by subjecting a compound [A] having a hydroxyl group or a primary or secondary amino group and a compound [B] having a phosphorous atom-containing substituent group of the general formula [1] to a condensation reaction, characterized in that the method is carried out in the presence of at least one reaction accelerator selected from the group consisting of a quaternary ammonium salt, a quaternary imidazolium salt, a quaternary morpholinium salt, a quaternary phosphonium salt, a quaternary piperidinium salt, a quaternary pyridinium salt, a quaternary pyrrolidinium salt and a quaternary sulfonium salt.

Disclosed are processes for preparing oligonucleotides. The process comprises: (a) converting a compound of Formula X-1 into a compound of Formula X-2: where R.sup.10 is a residue of an oligonucleotide (e.g., a phosphorodiamidate morpholino oligomer); R.sup.11 is an amine protecting group; wherein the compound of Formula X-1 is not bound to a solid support; and; (b) optionally removing protecting groups in the compound of Formula X-2 to obtain the olignucleotide. The synthetic processes described herein are advantageous in many aspects, including but not limited to improved yields and purities of target phosphorodiamidate morpholino oligomers with reduced 4-nitrostyrene adduct impurities. (X-1), (X-2)

##STR00001##

An organic compound is represented by general formula (1) below: ##STR00001## where X.sub.1 and X.sub.2 are each independently selected from the group consisting of an alkyl group, an aryl group, and an aralkyl group; R.sub.11 to R.sub.16 are each independently selected from the group consisting of a hydrogen atom, an alkyl group, an alkoxy group, an aryl group, a heterocyclic group, and a halogen atom; R.sub.21 and R.sub.22 are each independently selected from the group consisting of a hydrogen atom, an alkyl group, an aryl group, and an aralkyl group; and A.sub.1.sup.− and A.sub.2.sup.− each independently represent a monovalent anion.