Chemoenzymatic synthesis of the human CD52 and CD24 antigen analogues

Abstract

Analogs of the human CD52 and CD24 antigens carrying the common core structure of glycosylphosphatidylinositol (GPI) anchors and the intact polypeptide sequences of CD52 and CD24 were chemoenzymatically synthesized. CD52 and CD24 proteins were obtained by solid-phase peptide synthesis and then coupled to chemically synthesized GPI anchors under the influence of a bacterial enzyme, sortase A, to afford the target molecules in good yields.

Figure 1

GPI anchors 1 and 2 used to synthesize CD52 and CD24 analogs

Scheme 1

A general design for the synthesis of CD52 and CD24 analogs

Scheme 2

Synthesis of GPI anchors 1 and 2 Reaction conditions: (a) TMSOTf, Et₂O, −40 °C; (b) NaOMe, CH₂Cl₂/MeOH, 76% (over 2 steps); (c) PivCl, pyridine, rt; then I₂, pyridine/H₂O, 74%; (d) 5% TFA in CH₂Cl₂, 69%; (e) (1) PivCl, pyridine, rt; (2) I₂, pyridine/H₂O, 70%–72%; (f) H₂, 10% Pd(OH)₂/C, 76%–88%.

Scheme 3

SrtA-mediated synthesis of CD52 and CD24 analogs