Selective Desulfurization Significantly Expands Sequence Variety of 3′‐Peptidyl–tRNA Mimics Obtained by Native Chemical Ligation

Synthesis of aminoacylated N6,N6-dimethyladenosine solid support for efficient access to hydrolysis-resistant 3′-charged tRNA mimics

“… 23–27 More recent developments from our group have expanded the procedures to allow for site-specific methylation, phosphorylation and phosphonation of the RNA-peptide conjugates, 22 and beyond that, use native chemical ligation to increase amino acid side chain flexibility. 28,29 All of our approaches so far pass a 3′-azido-3′-deoxyadenosine derivative as key intermediate, as originally shown in 2009. 26 This intermediate allows to couple structurally diverse amino acids at a late stage of the synthesis, representing a significant advantage over most other synthetic strategies that make use of puromycin as key precursor, 11,30 thereby accepting the drawback that the amino acid at the junction is restricted to O -methylated tyrosine.…”

Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA

“…This has been particularly helpful for RNA structures [ 40 , 41 ]. Considerable progress has been made with combining tRNA and peptides [ 42 , 43 ], though scale up has been problematic and/or expensive. Continued efforts will help understand the intricate workings of Pth1 enzymes and hopefully fulfill their pharmacological potential.…”

Native Chemical Ligation of Hydrolysis‐Resistant 3′‐NH‐Cysteine‐Modified RNA

“…Soon after the pioneering work by Yan and Dawson (Yan and Dawson, 2001) who achieved this conversion through the action of Raney nickel or Pd/Al 2 O 3 , a metalfree version for cysteine thiol reduction was reported by Wan and Danishefsky (Wan and Danishefsky, 2007). An optimized version of the metal-free desulfurization method reported by Seitz and coworkers (Haase et al, 2008) can also be applied to cysteine-containing 3peptidyl-RNA conjugates to significantly extend their sequence variety (Geiermann and Micura, 2012). Cleavage/deprotection of 3 -NH-cysteinyl-RNA (a) 10 M CH 3 NH 2 in EtOH/H 2 O (1:1 v/v), 1 mL, 8 hr, room temperature (standard RNA deprotection) (b) 10 M CH 3 NH 2 in EtOH/H 2 O (1:1 v/v) (Pitsch et al, 2001) <20 nt: 0.5 mL, 3 hr, room temperature <50 nt: 1 mL, 4 hr, 35°C >50 nt: 1.5 mL, 6 hr, 35°C (c) 32% (v/v) NH 3 in H 2 O/8 M CH 3 NH 2 in EtOH (1:1 v/v), 1 mL, 10 min at 25°C, 10 min at 65°C (AMA deprotection) (Reddy et al, 1994) (Pitsch et al, 2001) <20 nt: 0.5 mL, 5 hr, 25°C <50 nt: 1 mL, 10 hr, 25°C >50 nt: 1.5 mL, 14 hr, 30°C (c) 1 M TBAF in THF/H 2 O (9:1 v/v) (Höbartner et al, 2004) <20 nt: 0.5 mL, 5 hr, 25°C <50 nt: 1 mL, 10 hr, 25°C >50 nt: 1.5 mL, 14 hr, 30°C (d) 1 M TBAF/0.5 M AcOH in THF <20 nt: 0.5 mL, 5 hr, 25°C <50 nt: 1 mL, 10 hr, 25°C >50 nt: 1.5 mL, 14 hr, 30°C…”

“…Soon after the pioneering work by Yan and Dawson (Yan and Dawson, ) who achieved this conversion through the action of Raney nickel or Pd/Al 2 O 3 , a metal‐free version for cysteine thiol reduction was reported by Wan and Danishefsky (Wan and Danishefsky, ). An optimized version of the metal‐free desulfurization method reported by Seitz and coworkers (Haase et al., ) can also be applied to cysteine‐containing 3′‐peptidyl‐RNA conjugates to significantly extend their sequence variety (Geiermann and Micura, ).…”