299430-87-8Relevant academic research and scientific papers
LIGAND-2'-MODIFIED NUCLEIC ACIDS, SYNTHESIS THEREOF AND INTERMEDIATE COMPOUNDS THEREOF
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Paragraph 00338; 00345, (2021/03/05)
The present invention relates to methods for synthesizing compounds useful as potent and stable RNA interference agents, derivatives thereof, and intermediates thereto.
RELEASABLE ANTIBODY CONJUGATES
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Page/Page column 91-92, (2019/10/01)
This document provides compounds of Formula (I), or pharmaceutically acceptable salts thereof, wherein D is a residue of a cytotoxic or chemotherapeutic compound, which undergoes hydrolysis under physiological conditions to release the cytotoxic or chemot
Hydrophilic and Cell-Penetrable Pyrrolidinyl Peptide Nucleic Acid via Post-synthetic Modification with Hydrophilic Side Chains
Pansuwan, Haruthai,Ditmangklo, Boonsong,Vilaivan, Chotima,Jiangchareon, Banphot,Pan-In, Porntip,Wanichwecharungruang, Supason,Palaga, Tanapat,Nuanyai, Thanesuan,Suparpprom, Chaturong,Vilaivan, Tirayut
, p. 2284 - 2292 (2017/09/26)
Peptide nucleic acid (PNA) is a nucleic acid mimic in which the deoxyribose-phosphate was replaced by a peptide-like backbone. The absence of negative charge in the PNA backbone leads to several unique behaviors including a stronger binding and salt independency of the PNA-DNA duplex stability. However, PNA possesses poor aqueous solubility and cannot directly penetrate cell membranes. These are major obstacles that limit in vivo applications of PNA. In previous strategies, the PNA can be conjugated to macromolecular carriers or modified with positively charged side chains such as guanidinium groups to improve the aqueous solubility and cell permeability. In general, a preformed modified PNA monomer was required. In this study, a new approach for post-synthetic modification of PNA backbone with one or more hydrophilic groups was proposed. The PNA used in this study was the conformationally constrained pyrrolidinyl PNA with prolyl-2-aminocyclopentanecarboxylic acid dipeptide backbone (acpcPNA) that shows several advantages over the conventional PNA. The aldehyde modifiers carrying different linkers (alkylene and oligo(ethylene glycol)) and end groups (-OH, -NH2, and guanidinium) were synthesized and attached to the backbone of modified acpcPNA by reductive alkylation. The hybrids between the modified acpcPNAs and DNA exhibited comparable or superior thermal stability with base-pairing specificity similar to those of unmodified acpcPNA. Moreover, the modified apcPNAs also showed the improvement of aqueous solubility (10-20 folds compared to unmodified PNA) and readily penetrate cell membranes without requiring any special delivery agents. This study not only demonstrates the practicality of the proposed post-synthetic modification approach for PNA modification, which could be readily applied to other systems, but also opens up opportunities for using pyrrolidinyl PNA in various applications such as intracellular RNA sensing, specific gene detection, and antisense and antigene therapy.
A versatile annulation protocol toward novel constrained phosphinic peptidomimetics
Nasopoulou, Magdalini,Georgiadis, Dimitris,Matziari, Magdalini,Dive, Vincent,Yiotakis, Athanasios
, p. 7222 - 7228 (2008/02/12)
(Chemical Equation Presented) The development of a novel 3-center 2-component annulation reaction between α,ω-carbamoylaldehydes and suitably monoalkylated phosphinic acids is reported. Depending on the starting α,ω-carbamoylaldehyde, diverse phosphinic scaffolds varying in the size of their rigidity element, the nature and stereochemistry of substituents, and the participation of heteroatoms in the azacyclic ring system can be obtained in one synthetic step and in high yield. In addition, this methodology allows the synthesis of Fmoc-protected constrained aminophosphinic acids that can be easily converted to suitable pseudodipeptide building blocks compatible with the requirements of peptide synthesis on the solid phase. Finally, the careful choice of both substituents and protecting groups can provide functionally diverse, orthogonally protected constrained scaffolds for extended derivatization of the target phosphinic peptidomimetic structrures.
