15231-21-7Relevant articles and documents
Catalytic activity of the N-terminal domain of Escherichia coli asparagine synthetase B can be reengineered by single-point mutation
Boehlein, Susan K.,Rosa-Rodriguez, José G.,Schuster, Sheldon M.,Richards, Nigel G. J.
, p. 5785 - 5791 (1997)
The development of mechanistic strategies for the modification of enzyme function is of considerable biotechnological interest. We now report that replacement of the catalytically important residue Asp-74 by aspartic acid (N74D) in the N-terminal domain of Escherichia coli asparagine synthetase B (AS-B) confers nitrile hydratase activity upon the mutant enzyme. Furthermore, while wild type AS-B can efficiently catalyze the hydrolysis of glutamine to glutamate, the N74D AS-B mutant exhibits very low glutaminase activity. These results are consistent with similar experiments on papain, supporting the hypothesis that mutation of a critical active site residue to affect the partitioning of an intermediate common to multiple reaction mechanisms may represent an approach by which enzymes can be obtained with different catalytic function. Our experiments also provide the first direct chemical evidence for a close mechanistic relationship between papain, a thiol protease, and AS-B, a class II Ntn amidotransferase. These enzymes are not likely to have arisen by evolution from a common ancestral protein.
S-2-Amino-4-cyanobutanoic acid (β-cyanomethyl-l-Ala) as an atom-efficient solubilising synthon for l-glutamine
Beauchard, Anne,Twum, Elvis A.,Lloyd, Matthew D.,Threadgill, Michael D.
supporting information; experimental part, p. 5311 - 5314 (2011/10/30)
Glutamine (Gln) is often a difficult amino acid to incorporate during solution-phase peptide synthesis, owing to poor solubility and unwanted dehydrations as side-reactions. Current approaches to solving these problems are highly atom-inefficient. Nα-Cbz-β-cyanomethyl-l-Ala is readily accessible by dehydration of Cbz-l-Gln. β-Cyanomethyl-l-Ala can be incorporated into short peptides easily by conventional methods. The nitrile is stable to the hydrogenolysis conditions used to remove Cbz and to acidic deprotection but is quantitatively hydrated to the γ-carboxamide of l-Gln with hydrogen peroxide. Thus β-cyanomethyl-l-Ala may represent a new, soluble, perfectly atom-efficient synthon for l-Gln.
Total synthesis of HUN-7293
Boger, Dale L.,Keim, Holger,Oberhauser, Berndt,Schreiner, Erwin P.,Foster, Carolyn A.
, p. 6197 - 6205 (2007/10/03)
The first total synthesis of the cyclic heptadepsipeptide HUN-7293 (1), a potent inhibitor of cell adhesion molecule expression exhibiting anti-inflammatory properties, is detailed. The most effective approach relied on an unusually efficient macrocyclization with the formation of the MLEU3 - LEU4 secondary amide that potentially benefits from intramolecular H-bonding preorganization of the acyclic substrate. The requisite linear depsipeptide was convergently assembled with the late stage introduction of the linking ester enlisting a Mitsunobu esterification that occurs with inversion of the DGCN α-center permitting the utilization of a readily available L-amino acid precursor to the D α-hydroxy carboxylic acid residue. An alternative and similarly attractive approach of direct macrolactonization of a substrate necessarily incorporating a D-DGCN subunit proved viable albeit less effective. Biological evaluation in cellular assays for vascular adhesion molecule expression confirmed that synthetic HUN-7923 (1) is essentially indistinguishable from the naturally occurring cyclodepsipeptide.
