192314-71-9Relevant articles and documents
Unsaturated α-aminopimelic acids as potent inhibitors of meso-diaminopimelic acid (DAP) D-dehydrogenase
Sutherland, Andrew,Caplan, Jennifer F.,Vederas, John C.
, p. 555 - 556 (1999)
Two nonproteinogenic amino acids 5 and 6 have been efficiently prepared using an S(H)2' allylstannane coupling reaction and a Wittig reaction, respectively, to effect the key steps; kinetic studies show these compounds to be reversible inhibitors of DAP dehydrogenase with K(i) values of 5.3 (competitive) and 44 μM (noncompetitive), respectively.
Structure-Activity Relationships for the Marine Natural Product Sintokamides: Androgen Receptor N-Terminus Antagonists of Interest for Treatment of Metastatic Castration-Resistant Prostate Cancer
Yan, Luping,Banuelos, Carmen A.,Mawji, Nasrin R.,Patrick, Brian O.,Sadar, Marianne D.,Andersen, Raymond J.
, p. 797 - 813 (2020/11/13)
Synthetic analogues of the marine natural product sintokamides have been prepared in order to investigate the structure-activity relationships for the androgen receptor N-terminal domain (AR NTD) antagonist activity of the sintokamide scaffold. An in vitro LNCaP cell-based transcriptional activity assay with an androgen-driven luciferase (Luc) reporter was used to monitor the potency of analogues. The data have shown that the chlorine atoms on the leucine side chains are essential for potent activity. Analogues missing the nonchlorinated methyl groups of the leucine side chains (C-1 and C-17) are just as active and in some cases more active than the natural products. Analogues with the natural R configuration at C-10 and the unnatural R configuration at C-4 are most potent. Replacing the natural propionamide N-terminus cap with the more sterically hindered pivaloylamide N-terminus cap leads to enhanced potency. The tetramic acid fragment and the methyl ether on the tetramic acid fragment are essential for activity. The SAR optimized analogue 76 is more selective, easier to synthesize, more potent, and presumed to be more resistant to proteolysis than the natural sintokamides.
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.
