52683-82-6Relevant academic research and scientific papers
Michael Addition of 2,2-Difluoroketene Silyl Acetal. Preparation of 4,4-Difluoroglutamic Acid and 5,5-Difluorolysine
Kitagawa, Osamu,Hashimoto, Akihiro,Kobayashi, Yoshiro,Taguchi, Takeo
, p. 1307 - 1310 (2007/10/02)
2,2-Difluoroketene Silyl Acetal, generated in situ by treating methyl difluoroiodoacetate with Zn followed by chlorosilane, readily reacted with α,β-unsaturated carbonyl compounds or acetals to give the 1,4-addition products, preferentially.The difluoro a
Potential inhibitors of collagen biosynthesis. 5,5-Difluoro-DL-lysine and 5,5-dimethyl-DL-lysine and their activation by lysyl-tRNA ligase
Shirota,Nagasawa,Elberling
, p. 1623 - 1627 (2007/10/05)
The synthesis of lysine analogues wherein blocking groups are substituted at position 5, the site of hydroxylation by peptidyl lysine hydroxylase, is described. Thus, 5,5-diflurolysine (1) and 5,5-dimethyllysine (2) were synthesized via a four- and six-step sequence, respectively, starting from ketone precursors. The propensity for these lysine analogues to be incorporated into procollagen protein in vivo was assessed by their ability to stimulate the lysine-dependent ATP-PP(i) exchange reaction in the presence of lysyl-tRNA ligase in vitro. The difluoro analogue 1 stimulated exchange, but at a K(m) (1.3 x 10-3 M) 1000 times greater than that for lysine itself. The dimethyl analogue 2 did not stimulate exchange, but at high concentrations was a competitive inhibitor of lysine, with an apparent K(i) of 1.6 x 10-2 M. Thus, electronegative and/or bulky substituents at the 5 position of lysine cannot be tolerated by lysyl-tRNA ligase, and this position must be kept free in lysine analogues specifically designed to block collagen biosynthesis.
