Abstract: Disclosed are a cyclic dinucleotide prodrug molecule, a preparation method therefor and an application thereof relating to the field of pharmaceuticals. The cyclic dinucleotide prodrug molecule has a structure shown in formula I, II, or III, can freely cross cell membranes and release cyclic dinucleotide, and has high cell activity.

Abstract: The present disclosure belongs to the technical field of biomedicine, and specifically relates to a PSMA inhibitor, compound and use thereof. The PSMA inhibitors having a novel core structure provided in the present disclosure has a wide range of potential applications.

Abstract: Disclosed are a cyclic dinucleotide prodrug molecule, a preparation method therefor and an application thereof relating to the field of pharmaceuticals. The cyclic dinucleotide prodrug molecule has a structure shown in formula I, II, or III, can freely cross cell membranes and release cyclic dinucleotide, and has high cell activity.

Abstract: A single valve compression release bridge brake is provided. The single valve compression release bridge brake includes a braking piston (160) integrated into an inner end of a valve bridge (400) which is located under a rocker arm (210) of an engine. The braking piston (160) is slidably disposed in a braking piston bore (190) opened downwards from the inner end of the valve bridge (400). The lower end of the braking piston (160) is connected to the inner exhaust valve (3001). Oil is supplied to the braking piston bore (190) in the valve bridge (400). The inner end of the valve bridge (400) above the braking piston (160) is pushed upwards against the rocker arm (210) by oil pressure, and a hydraulic linkage is formed between the braking piston (160) and the valve bridge (400).

Abstract: Nucleotide and/or oligonucleotide represented by formula (1) and the liquid phase synthesis process thereof. The present invention provides a liquid phase synthesis process for preparing a nucleotide and/or an oligonucleotide, comprising a process for combining the nucleotide and/or oligonucleotide protective groups, in which, under the condition that the 2?-hydroxyl group is protected by a group with a sterically hindered silane structure, the 3? phosphate group(s) of the nucleotide and/or oligonucleotide is/are directly protected by (a)?-cyanoethyl group(s), and after the ?-cyanoethyl group(s) is/are removed, the resulting product can directly participate in the next cycle of synthesis, wherein the synthesis reaction is carried out in a reaction flask or reaction kettle, without being limited by a solid carrier or synthesizer, so that the large scale preparation of oligonucleotides can be achieved.

Abstract: A method for preparing oligonucleotide comprising reacting the compound of Formula (1) with the compound of Formula (2) in a liquid reaction medium under the condition of condensation reaction to obtain the compound of formula (3) is provided. 1-(2-mesitylenesulfonyl)-3-nitro-1H-1,2,4-triazole (MSNT) is applied as condensing agent. Oligonucleotides synthesized in the liquid reaction medium could be obtained on a large scale.

Abstract: Nucleotide and/or oligonucleotide represented by formula (1) and the liquid phase synthesis process thereof. The present invention provides a liquid phase synthesis process for preparing a nucleotide and/or an oligonucleotide, comprising a process for combining the nucleotide and/or oligonucleotide protective groups, in which, under the condition that the 2?-hydroxyl group is protected by a group with a sterically hindered silane structure, the 3? phosphate group(s) of the nucleotide and/or oligonucleotide is/are directly protected by (a)?-cyanoethyl group(s), and after the ?-cyanoethyl group(s) is/are removed, the resulting product can directly participate in the next cycle of synthesis, wherein the synthesis reaction is carried out in a reaction flask or reaction kettle, without being limited by a solid carrier or synthesizer, so that the large scale preparation of oligonucleotides can be achieved.

Abstract: A method for preparing oligonucleotide comprising reacting the compound of Formula (1) with the compound of Formula (2) in a liquid reaction medium under the condition of condensation reaction to obtain the compound of formula (3). In the method according to the present invention, the functional groups are protected by suitable protective groups to only expose the 5?-OH of the compound of Formula (1) (OH-component) and the 3?-phosphate of the compound of Formula (2) (P-component) which are to be connected, so that the condensation reaction is carried out in a liquid reaction medium to bond the OH-component and P-component to obtain DNA or RNA short chain. The method of the present invention does not need a solid phase column and can be carried out in a liquid reaction medium. Thus, oligonucleotides can be synthesized on a large scale.

Abstract: The present invention provides a complex molecule interfering the expression of target genes and the methods for preparing the complex molecule, wherein the complex molecule contains two siRNA strands X1 and X2 having at least 80% complementarity, the 5? end of X1 and 3? end of X2 are linked through non-nucleic acid molecule L1, the 5? end of X2 and 3? end of X1 are linked through non-nucleic acid molecule L2. Since both 5? and 3? ends of two siRNA strands X1 and X2 of the complex molecule according to the present invention are linked through non-nucleic acid molecules, it is not easy to unwind and degraded for the siRNA strands, and therefore the chemical stability of siRNA and the remaining time in the blood are greatly improved. After being administered, the Dicer enzyme in the cells is utilized to release the locked siRNAs from the complex molecules, and after unwinding, the antisense strand of the siRNA is released from the double-stranded siRNA to inhibit the expression of the target genes.