21075-83-2Relevant articles and documents
Design, Synthesis, and Characterization of Cyclic Peptidomimetics of the Inducible Nitric Oxide Synthase Binding Epitope That Disrupt the Protein-Protein Interaction Involving SPRY Domain-Containing Suppressor of Cytokine Signaling Box Protein (SPSB) 2 and Inducible Nitric Oxide Synthase
Harjani, Jitendra R.,Yap, Beow Keat,Leung, Eleanor W. W.,Lucke, Andrew,Nicholson, Sandra E.,Scanlon, Martin J.,Chalmers, David K.,Thompson, Philip E.,Norton, Raymond S.,Baell, Jonathan B.
, p. 5799 - 5809 (2016)
SPRY domain-containing suppressor of cytokine signaling box protein (SPSB) 2-deficient macrophages have been found to exhibit prolonged expression of inducible nitric oxide synthase (iNOS) and enhanced killing of persistent pathogens, suggesting that inhibitors of the SPSB2-iNOS interaction have potential as novel anti-infectives. In this study, we describe the design, synthesis, and characterization of cyclic peptidomimetic inhibitors of the SPSB2-iNOS interaction constrained by organic linkers to improve stability and druggability. SPR, ITC, and 19F NMR analyses revealed that the most potent cyclic peptidomimetic bound to the iNOS binding site of SPSB2 with low nanomolar affinity (KD 29 nM), a 10-fold improvement over that of the linear peptide DINNN (KD 318 nM), and showed strong inhibition of SPSB2-iNOS interaction in macrophage cell lysates. This study exemplifies a novel approach to cyclize a Type II β-turn linear peptide and provides a foundation for future development of this group of inhibitors as new anti-infectives.
WEE1 KINASE INHIBITORS AND METHODS OF TREATING CANCER USING THE SAME
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Page/Page column 39-40, (2019/09/18)
A compound, or a pharmaceutically acceptable salts or prodrugs thereof, having the chemical structure (I) and methods of using these compounds to inhibit WEE1 kinase and treat cancer in a subject.
Synthetic method of Fmoc-Aza-beta 3-Ala
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Paragraph 0033; 0034, (2018/07/07)
The invention discloses a synthetic method of Fmoc-Aza-Beta 3-Ala. The method comprises the following steps: processing methylhydrazine by utilizing excessive di-tert-butyl dicarbonate ester to obtaina compound 1 as shown in formula B1, Fmoc-cl and NaHCO3 are added into the compound 1 shown in the formula B1 to have nucleophilic substitution to obtain a compound 2 as shown in formula B2, the compound 2 as shown in the formula B2 is obtained by virtue of the acidification of trifluoroacetic acid (TFA) or HCLG, so that a Boc protection group is broken to obtain a compound 3 as shown in formulaB3; the compound 3 as shown in the formula B3 is enable to have nucleophilic substitution with tert-butyl bromoacetate to obtain a compound 4 as shown in formula A4; and the compound 4 as shown in theformula A4 is enabled to have degreasing reaction with dichloromethane introduced with HCl gas to obtain a target product Fmoc-Aza-Beta 3-Ala as shown in formula B5. The preparation method provided by the invention is mild in reaction condition, the Fmoc protection group can be easily removed by utilizing a mild alkaline condition, the operation is simple, the acid instable group can be used forprotecting a side chain, and a route is simple and efficient.
