109608-77-7Relevant articles and documents
Gem-dimethyl peptide nucleic acid (α/β/γ-gdm-PNA) monomers: synthesis and the role ofgdm-substituents in preferential stabilisation ofZ/E-rotamers
Datta, Dhrubajyoti,Ganesh, Krishna,Kulkarni, Pradnya,Ramabhadran, Raghunath O.
, p. 6534 - 6545 (2021/08/03)
The flexible backbone of aminoethylglycine (aeg) PNA upon substitution becomes sterically constrained to enable conformational pre-organization for preferential binding to DNA or RNA. The bulkygem-dimethyl (gdm) substituent on carbons adjacent to thet-amide sidechain either at Cα (glycyl) or Cβ/Cγ (aminoethylene) sides may influence theZ/Erotamer ratio arising from a restricted rotation around thet-amide bond. Employing 2D NMR (NOESY), it is shown here that the Cα-gdm-PNA-T monomer exhibits exclusively theZ-rotamer, while the Cβ-gdm-PNA-T monomer shows only theE-rotamer. The unsubstitutedaeg-PNA-T and Cγ-gdm-PNA-T monomers display a mixture ofZ/Erotamers. The rotamers witht-amide carbonyl pointing towards thegem-dimethyl group always prevailed. The results are supported by computational studies that suggested that the preferred rotamers are the outcome of a net energetic benefit from the stabilising n-π* interactions of carbonyls (amide backbone andt-amide sidechain), and C-H?O interactions and the destabilising steric clash ofgem-dimethyl groups with the t-amido methylene group. TheE-rotamer structure in Cγ-gdmis also characterised by X-ray crystallography. The exclusiveE-rotamer for the Cβ-gdmmonomer seen in solution here is the first such example among several modified PNA monomers. Since the conformation of the sidechain is important for inducing base stacking and effective base pairing, the exclusiveE-rotamer in the Cβ-gdmmonomer may have significance in the properties of the derived PNA?:?DNA/RNA duplexes with allE-rotamers.
Vinyl Sulfone-Based Inhibitors of Nonstructural Protein 2 Block the Replication of Venezuelan Equine Encephalitis Virus
Zhang, Huaisheng,Harmon, Moeshia,Radoshitzky, Sheli R.,Soloveva, Veronica,Kane, Christopher D.,Duplantier, Allen J.,Ogungbe, Ifedayo Victor
, p. 2139 - 2145 (2020/12/17)
Emerging infectious diseases like those caused by arboviruses such as Venezuelan equine encephalitis virus (VEEV) pose a serious threat to public health systems. Development of medical countermeasures against emerging infectious diseases are of utmost importance. In this work, an acrylate and vinyl sulfone-based chemical series was investigated as promising starting scaffolds against VEEV and as inhibitors of the cysteine protease domain of VEEV's nonstructural protein 2 (nsP2). Primary screen and dose response studies were performed to evaluate the potency and cytotoxicity of the compounds. The results provide structural insights into a new class of potent nonpeptidic covalent inhibitors of nsP2 cysteine protease represented by compound 11 (VEEV TrD, EC50= 2.4 μM (HeLa), 1.6 μM (Vero E6)). These results may facilitate the evolution of the compounds into selective and broad-spectrum anti-alphaviral drug leads.
ANTIMICROBIAL COMPOUNDS AND METHODS
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Paragraph 00447, (2020/07/31)
The invention is directed to compounds that are active as antibacterial agents. The invention compounds are active against gram-positive and gram-negative bacteria and can be used to treat infections caused by gram-positive and gram-negative bacteria. Also disclosed are processes and intermediates for making the compounds.