Figure 3: Solid phase synthesis of bicyclic peptides by means of the RCM/RCAM method. | Nature Communications

Figure 3: Solid phase synthesis of bicyclic peptides by means of the RCM/RCAM method.

From: Orthogonal ring-closing alkyne and olefin metathesis for the synthesis of small GTPase-targeting bicyclic peptides

Figure 3

(a) General scheme for the synthesis of bicyclic peptides obtained by means of RCM and RCAM of the acyclic precursor peptides. (j=2, number of C-terminal amino acids; R=side chain of a proteinogenic amino acid except Cys or Met). (b) Sequence of bicyclic test peptide 16 bearing an i,i+4 olefin crosslink (eight C-atoms) and an i,i+4 alkyne crosslink (nine C-atoms). Chromatograms of crude reaction mixtures of peptide 16 before macrocyclization (13, top), after RCAM (14, second) and RCM (15, third), respectively, and after simultaneous (one-pot) RCM and RCAM (16, bottom). Corresponding product peaks are highlighted: fully open (13, blue), alkyne monocycle (14, red), olefin monocycle (15, orange) and bicyclic peptide (16, green). Chromatograms were obtained after deprotection and cleavage of resin-bound intermediates. ‘l’ represents Complex 5, dry toluene, 40 °C, 2 × 1.5 h; ‘m’ represents Grubbs first-generation catalyst, DCE, 3 × 2 h; ‘n’ represents Complex 5, Grubbs first-generation catalyst, dry toluene, 40 °C, 2 × 1.5 h.

Back to article page