Science of Synthesis

Farrera-Soler, L.; Vummidi, B. R.; Barluenga, S.; Winssinger, N., Science of Synthesis: DNA-Encoded Libraries, (2024) 1, 543.

The synthesis of the PNA-peptide conjugates was performed with an automated Intavis AG Multipep RS instrument. In brief, NovaPEG Rink Amide resin (5.0 mg; 0.44 mmol · g−1 loading) was added into microcolumns, and iterative cycles of deprotection of the desired protecting group [either 20% piperidine in DMF for Fmoc deprotection, or HOBt (244 mg) in 1,2-dichloroethane/HFIP (1:1; 20 mL) for MTT deprotection], amide coupling [monomer (4.0 equiv), HATU (3.5 equiv), and iPr2NEt (5.0 equiv) in NMP], and capping of the resin [AcOH (0.92 mL) and 2,6-lutidine (1.3 mL) in DMF (18 mL)] were performed to couple each building block. Finally, the PNA-peptide conjugate was deprotected and cleaved from the resin by treatment with a cleavage solution [phenol (25 mg), H2O (25 µL), and (iPr)3SiH (10 µL) in TFA (440 µL)] for 2 h and precipitated with Et2O. After centrifugation, the pellet was lyophilized and dissolved in DMSO to give the final stock solution.[‌15‌]

References