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Updated: Aug 18, 2026

Solid Phase Synthesis of a Functionalized Bis-Peptide Using "Safety Catch" Methodology
Published on: May 15, 2012
Combined solid-phase/solution synthesis of large ribonuclease A C-terminal peptides containing a non-natural proline
1Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853-1301, USA.
Abstract:
Three large peptides corresponding to the 65-124 (60-mer), 72-124 (53-mer), and 77-124 (48-mer) sequence of bovine pancreatic ribonuclease A (RNase A) were assembled from either two or three shorter protected peptide fragments by chemical coupling in solution. The fragments were synthesized manually by 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase peptide chemistry in plastic syringes, and subsequently purified by normal-phase high-performance liquid chromatography on a silica gel column. The main aim of this work was to incorporate sterically hindered l-5,5-dimethylproline (dmP) as a substitute for Pro(93) into the sequence of RNase A in order to constrain the -Tyr(92)-Pro(93)- peptide group to a single cis-conformation.
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