α-Galactosyl epitopes are carbohydrate structures bearing a Galα1-3Galβ terminus. The interaction of these epitopes on the surface of animal cells with anti-α-galactosyl antibodies in human serum is believed to be the main cause in antibody-mediated hyperacute rejection in xenotransplantation. This report describes an efficient chemoenzymatic approach based on the use of recombinant α(1→3)-galactosyltransferase (α1,3-GalT) for the synthesis of xenoactive α-galactosyl epitopes, which are highly desired in the research of xenotransplantation and immunotherapy. A truncated bovine α1,3-GalT (80−368) was cloned into the pET15b vector and subsequently transformed into E. coli BL21 strain. This expression system efficiently produced the soluble recombinant enzyme on a large scale with highly specific activity. A variety of α(1→3)-galactosylated epitopes were synthesized using such a recombinant enzyme. In a unique fashion, α-galactosyl pentasaccharide was synthesized via a one-pot, two-step enzymatic synthesis with in situ cofactor regeneration.

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The enzyme protein-farnesyl transferase (FTase) catalyzes the farnesylation of the Ras protein and other key signal transduction proteins, using farnesyl diphosphate (FPP) as the prenyl source. Inhibitors of FTase are thus of great interest as potential novel anticancer agents. The design of such agents would be informed by a detailed knowledge of the solution conformation of FPP, as well as its conformation in the active site of FTase. Four bis-13 C-labeled derivatives of farnesol and geranylgeraniol have been synthesized and used to prepare the corresponding FPP and GGPP derivatives. The labeled farnesyl and geranylgeranyl derivatives 2-7 were utilized in conjunction with solution 13 C NMR to probe the conformation of the prenyl chain in a variety of different solvents. These studies, along with molecular dynamics simulations, demonstrate that the prenyl chain exists primarily in an extended conformation. Surprisingly, this preference for the extended conformation is solvent-insensitive; no significant change in conformation is seen with all six solvents investigated, including water. The [6,15-bis 13 C]FPP analogue 8 was complexed with mammalian FTase, and this complex was utilized in conjunction with rotational resonance MAS NMR to investigate the prenyl chain conformation when bound in the active site of this enzyme. The conformation determined from these experiments is in good agreement with the structure determined from crystallographic studies on the FPP-FTase complex. Thus, the isoprenyl chain of FPP exhibits a strong preference for an extended conformation, both in a variety of solvents of different polarities and in the active site of mammalian FTase.The mevalonate pathway, both the main trunk and its various branch points, has been the subject of intense pharmaceutical, biochemical, and chemical research activity. 1 The chemical mechanisms of steroid and terpene cationic cyclization reactions have been the subjects of long-standing and intensive research interest from bioorganic and biological chemists. [2][3][4][5] The recent

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