6525-53-7Relevant articles and documents
Exploring the ability of dihydropyrimidine-5-carboxamide and 5-benzyl-2,4-diaminopyrimidine-based analogues for the selective inhibition of L. major dihydrofolate reductase
Bibi, Maria,Qureshi, Naveeda Akhter,Sadiq, Abdul,Farooq, Umar,Hassan, Abbas,Shaheen, Nargis,Asghar, Irfa,Umer, Duaa,Ullah, Azmat,Khan, Farhan A.,Salman, Muhammad,Bibi, Ahtaram,Rashid, Umer
, (2020/11/16)
To tackle leishmaniasis, search for efficient therapeutic drug targets should be pursued. Dihydrofolate reductase (DHFR) is considered as a key target for the treatment of leishmaniasis. In current study, we are interested in the design and synthesis of selective antifolates targeting DHFR from L. major. We focused on the development of new antifolates based on 3,4-dihydropyrimidine-2-one and 5-(3,5-dimethoxybenzyl)pyrimidine-2,4-diamine motif. Structure activity relationship (SAR) studies were performed on 4-phenyl ring of dihydropyrimidine (26–30) template. While for 5-(3,5-dimethoxybenzyl)pyrimidine-2,4-diamine, the impact of different amino acids (valine, tryptophan, phenylalanine, and glutamic acid) and two carbon linkers were explored (52–59). The synthesized compounds were assayed against LmDHFR. Compound 59 with the IC50 value of 0.10 μM appeared as potent inhibitors of L. major. Selectivity for parasite DHFR over human DHFR was also determined. Derivatives 55–59 demonstrated excellent selectivity for LmDHFR. Highest selectivity for LmDHFR was shown by compounds 56 (SI = 84.5) and 58 (SI = 87.5). Compounds Antileishmanial activity against L. major and L. donovani promastigotes was also performed. To explore the interaction pattern of the synthesized compounds with biological macromolecules, the docking studies were carried out against homology modelled LmDHFR and hDHFR targets.
Selenolysine: A New Tool for Traceless Isopeptide Bond Formation
Dardashti, Rebecca Notis,Kumar, Shailesh,Sternisha, Shawn M.,Reddy, Post Sai,Miller, Brian G.,Metanis, Norman
supporting information, p. 4952 - 4957 (2020/04/07)
Despite their biological importance, post-translationally modified proteins are notoriously difficult to produce in a homogeneous fashion by using conventional expression systems. Chemical protein synthesis or semisynthesis offers a solution to this problem; however, traditional strategies often rely on sulfur-based chemistry that is incompatible with the presence of any cysteine residues in the target protein. To overcome these limitations, we present the design and synthesis of γ-selenolysine, a selenol-containing form of the commonly modified proteinogenic amino acid, lysine. The utility of γ-selenolysine is demonstrated with the traceless ligation of the small ubiquitin-like modifier protein, SUMO-1, to a peptide segment of human glucokinase. The resulting polypeptide is poised for native chemical ligation and chemoselective deselenization in the presence of unprotected cysteine residues. Selenolysine's straightforward synthesis and incorporation into synthetic peptides marks it as a universal handle for conjugating any ubiquitin-like modifying protein to its target.
Method for synthesizing glutamic acid-1-methyl ester-5-tert-butyl ester
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Paragraph 0021; 0022, (2019/04/13)
The invention discloses a method for synthesizing glutamic acid-1-methyl ester-5-tert-butyl ester. The method comprises the following steps: generating dimethyl glutamate by using glutamic acid as aninitial raw material in methyl alcohol under the effect of thionyl chloride; reacting the dimethyl glutamate with triphenylchloromethane to generate dimethyl glutamate with triphenylmethyl protected amino; taking off methyl ester on the 5 position of the dimethyl glutamate with triphenylmethyl protected amino under the effect of sodium hydroxide to generate triphenylmethyl-glutamic acid-1-methyl ester; reacting the triphenylmethyl-glutamic acid-1-methyl ester-5-tert-butyl ester with trichloroacetic imine tert-butyl ester to generate triphenylmethyl-glutamic acid-1-methyl ester-5-tert-butyl ester, adding a small amount of triisopropylsilane into the triphenylmethyl-glutamic acid-1-methyl ester-5-tert-butyl ester in a low-concentration dichloromethane trifluoroacetate solution to take off triphenylmethyl to generate the glutamic acid-1-methyl ester-5-tert-butyl ester. The method is simple in operation, has few byproduct which can be extremely easy to treat and high product yield, and cansolve the problem of large operation difficulty in an existing synthesizing method.