Oligomers automated synthesis

F. Morvan, A. Meyer, A. Jochum, C. Sabin, Y. Chevolot, A. Imberty, J.-P. Praly, J.-J. Vasseur, E. Souteyrand, and S. Vidal, Fucosylated pentaerythrityl phosphodiester oligomers (PePOs) Automated synthesis of DNA-based glycoclusters and binding to Pseudomonas aeruginosa lectin (PA-IIL), Biocon-jug. Chem., 18 (2007) 1637-1643. 

Richter LS, Spellmeyer DC, Martin EJ, Figliozzi GM, Zuckermann RN. Automated synthesis of nonnatural oligomer h-braries the peptoid concept. Combinatorial Peptide and Nonpeptide Libraries. Jung G, ed. 1996. VCH, Weinheim, Germany, pp. 387 04. 

The PNA chain was linked to the peptide spacer glutamic acid-(y-tert-butyl ester)-(fi-aminohexanoic acid)-(fi-aminohexanoic acid) (Glu [OtBuj-fiAhx-fiAhx) via an enzymatically cleavable Glu-Lys handle. The Glu [OtBuj-fiAhx-fiAhx spacer was coupled to the amino-functionalized membrane by standard Fmoc-Chemistry. Then the membranes were mounted in an ASP 222 Automated SPOT Robot and a grid of the desired format was dispensed at each position. The free amino groups outside the spotted areas were capped and further chain elongation was performed with Fmoc-protected PNA monomers to synthesize the desired PNA oligomers (18). After completion of the synthesis, the PNA oligomers were cleaved from the solid support by incubation with bovine trypsin solution in ammonium bicarbonate at 37 °C for 3 h. 

SCHEME 10.14 Automated solid-phase assembly and synthesis of HA oligomers. 

We described an unusual oligomer whereby a-amino acids were converted into a-hydroxy acids by oxidative deamination with retention of stereochemistry, followed by reduction to 1,2-diols. The primary alcohol was protected by the dimethoxytrityl group, and the remaining secondary alcohol converted to a phos-phitylating agent. These monomers could then be incorporated into oligomers under the standard conditions of automated DNA synthesis. The resulting molecules retain amino acid side-chains, but have the phosphodiester backbone more familiar to nucleic acids. 

Scheme 7.6. Scheme for the automated parallel synthesis of poly-N-acylated amines exemplified for one defined compound, e.g., PAA oligomer 12 exhibiting high binding affinity to MHC class 1 molecule H-2Kb [49]. 

---