Chemoenzymatic-Chemical Synthesis of a (2-3)-Sialyl T Threonine Building Block and Its Application to the Synthesis of the N-Terminal Sequence of Leukemia-Associated Leukosialin (CD 43)

Abstract

Protection of all functional groups of the carbohydrate portion of the chemoenzymatically synthesized sialyl T threonine ester 1 (R=R1=H, R2=tBu, Fmoc=9‐fluorenylmethoxycarbonyl) and subsequent acidolysis of the tert‐butyl ester afforded the building block 2 (R=Ac, R1=Me, R2=H). The latter is a useful tool in the solid‐phase synthesis of the N‐terminal sequence 3 of the leukemia‐associated leukosialin.

Synthetic Glycopeptides from the Mucin Family as Potential Tools in Cancer Immunotherapy

“…The advantage of using a chemoenzymatic approach is that enzymatically catalyzed reactions usually proceed with both high regio-and stereoselectivity and therefore, eliminates the need for complicated protecting group manipulations. The successful enzyme-catalyzed synthesis of a 2,3-sialyl-T building block [164,165] is a good example of such a chemoenzymatic approach. The T N derivative (12) was used as the acceptor in this procedure (Fig.…”

“…. Chemoenzymatic synthesis of 2,3-ST-building block[164,165]. (a) lactose, β-galactosidase (bovine testes), CMP-NeuNAc, α-2,3-sialyltransferase, alkaline phosphatase (calf instestine), 2,6-di-O-methyl-β-cyclodextrin, BSA, pH 6.5, 50% (b) 1.…”

Chemo-enzymatic synthesis of C-9 acetylated sialosides

“…Next, the azido moiety of 8 was converted into an acetamido derivative by reaction with thioacetic acid in pyridine [33][34][35] and the resulting compound 9 was treated with a mixture of TFA and water to remove the t-butyl ester, and then with NaOMe in methanol to cleave the acetyl esters to give glycopeptide 10. 36 At this stage of the synthesis, the Cbz group was kept intact because protection of the amino group of serine is required for glycopeptide synthesis.…”

Chemoenzymatic Synthesis of a MUC1 Glycopeptide Carrying Non-Natural Sialyl TF-βO-Glycan

“…Tel: +81-463-50-2075; Fax: +81-463-50-2012; E-mail: yonak@keyaki.cc.u-tokai.ac.jp or hojo@keyaki.cc.u-tokai.ac.jp Abbreviations: BSA, bovine serum albumin; CMP-sialic acid, cytidine 5 0 -(5-acetamido-3,5-dideoxy-D-glycero--D-galacto-non-2-ulopyranosylonic acid monophosphate); DIEA, N,N-diisopropylethylamine; DMS, dimethylsulfide; Fmoc, 9-fluorenylmethoxycarbonyl; HBTU, O-benzotriazol-1-yl-N,N,N 0 ,N 0 -tetramethyluronium hexafluorophosphate; HOBt, 1-hydroxybenzotriazole; MS, mass spectrometry; MAb, monoclonal antibody; NMP, 1-methyl-2-pyrolidinone; Pbf, 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl; SPPS, solid-phase peptide synthesis; TFA, trifluoroacetic acid;TF-, -linked Thomsen-Friedenreich antigen; TfOH, trifluoromethanesulfonic acid; Trt, triphenylmethyl corresponding natural -trisaccharide has previously been synthesized by a fully chemical or chemoenzymatic method to use as building blocks for the solidphase synthesis of sialoglycopeptides by this group 7,8) and by others. 16,17) On the other hand, the related disaccharide, -D-Gal-(1!3)--D-GalNAc-Ser/Thr (TF-), had been synthesized by us to use in the epitope analysis of the colon carcinoma specific MAb, BW494, exhibiting cross-reactivity with -D-Gal-(1!3)--DGlcNAc (type 1 chain) and TF-. 18) In respect of the MUC1 glycopeptides carrying natural O-glycans, several groups have reported their synthetic efforts.…”