485800-27-9

Upstream product

• 67385-09-5 2-[(tert-butoxycarbonyl)amino]-1-ethanethiol 
• 107-96-0 3-mercaptopropionic acid 
• 68617-64-1 3-(2-pyridyldithio)propionic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 15579-00-7 3-<(2-aminoethyl)dithio>propionic acid 
• 67385-10-8 di-tert-butyl(disulfanediylbis(ethane-2,1-diyl))dicarbamate 

Downstream Products

• 1246813-56-8 C₄₄H₅₁N₇O₇S₂ 
• 1301262-95-2 2,3,5,6-tetrafluorophenyl 3-((2-(tert-butoxycarbonylamino)ethyl)disulfanyl)propanoate 
• 811442-78-1 C₂₁H₃₉N₅O₅S₃ 

Relevant academic research and scientific papers

In vivo delivery of RNAi by reducible interfering nanoparticles (iNOPs)

RNA interference (RNAi) has considerable potential as a therapeutic strategy, but the development of efficient in vivo RNA delivery methods remains challenging. To this end, we designed and synthesized chemically modified interfering nanoparticles (iNOPs) composed of functionalized poly-l-lysine dendrimers modified with reducible spacers to facilitate release of small interfering RNAs (siRNAs) in vivo. We show that the novel siRNA-iNOP complexes mediate efficient gene-specific RNAi in cultured cells and in mice, where they display enhanced tissue-targeting capabilities. At a clinically feasible dose of 1 mg kg-1, apolipoprotein B (apoB) siRNA-iNOP complexes achieved ～40-45% reduction of liver apoB mRNA and plasma apoB protein levels within 48 h of administration to mice, without apparent toxicity. Collectively, these findings demonstrate that siRNA delivery by the modified reducible iNOPs can provide a clinically significant and potentially tissue-specific new approach for RNAi therapy.

METHODS OF CHEMOTYPE EVOLUTION

Herein is described a method to rapidly screen a large chemical space for a compound that binds to a target protein through an iterative fragment assembly approach that can be performed at low reagent cost and without requiring purification of the assembled product. The method employs a library of test ligands each of which comprise a ‘bait’ molecule, which is known from prior art or prior screening to have some intrinsic affinity for the target protein, and a test moiety.

Design, synthesis and preliminary biological evaluation of a biotin-s-s-phosphine reagent

Biotin-S-S-Phosphine was designed and synthesized as a potential tool for a proteomic study of O-GlcNAcmodified proteins. This reagent features a disulfide linker between a triarylphosphine moiety, which allows selective conjugation to azide-containing proteins, and a biotin moiety that can allow easy isolation through its strong affinity toward avidin-coated solid beads. The disulfide linkage within this reagent can allow the easy release of the bound molecules of interest, which is difficult to achieve when a biotin:avidin pair is used alone, by reducing the disulfide bond of the reagent with DTT. Preliminary in vitro biological assays with azidelabeled and unlabeled cell lysates and a pure protein Nup62 showed that the Biotin-S-S-Phosphine reagent is highly reactive toward the free thiol groups of proteins. When a molecular tool with a disulfide linker is applied to the enrichment of the molecules of interest from other species, it is important to block the free-thiols of the sample using exhaustive alkylation prior to the Staudinger ligation reactions to restore the bioorthogonal nature of this reaction.

Metal complex mediated conjugation of peptides to nucleus targeting acridine orange: A modular concept for dual-modality imaging agents

To target the nucleus of specific cells, trifunctional radiopharmaceuticals are required. We have synthesized acridine orange derivatives which comprise an imidazole-2-carbaldehyde function for coordination to the [Re(CO)3]+ or [99mTc(CO)3]+ core. Upon coordination, this aldehyde is activated and rapidly forms imines with amines from biological molecules. This metal-mediated imine formation allows for the conjugation of a nuclear targeting portion with a specific cell receptor binding function directly on the metal. With this concept, we have conjugated the acridine orange part to a bombesin peptide directly on the 99mTc core and in one step. In addition, a linker containing an integrated disulfide has been coupled to bombesin. LC/MS study showed that the disulfide was reductively cleaved with a 60 min half-life time. This concept enables the combination of a nucleus targeting agent with a specific cell receptor molecule directly on the metal without the need of separate conjugation prior to labeling, thus, a modular approach. High uptake of the BBN conjugate into PC-3 cells was detected by fluorescence microscopy, whereas uptake into B16BL6 cells was negligible.

REAGENTS FOR REVERSIBLY TERMINATING PRIMER EXTENSION

This invention relates to the field of nucleic acid chemistry, more specifically to the field of compositions of matter that comprise triphosphates of modified 2'-deoxynucleosides and oligonucleotides that are formed when these are appended to the 3'-end of a primer, wherein said modifications comprise NH2 moiety attached to their 3'-hydroxyl group and a fluorescent species in a form of a tag affixed to the nucleobase via a linker that can be cleaved. Such compositions and their associated processes enable and improve the sequencing of oligonucleotides using a strategy of cyclic reversible termination, as outlined in US Patent 6,664,079. Most specifically, the invention concerns compositions of matter that are 5'-triphosphates of ribo- and 2'- deoxyribonucleosides carrying detectable tags and oligonucleotides that might be derived from them. The invention also concerns processes wherein a DNA polymerase, RNA polymerase, or reverse transcriptase synthesizes said oligonucleotides via addition of said triphosphates to a primer.