Related Experiment Video
Updated: Oct 24, 2026

Targeted Antibody Blocking by a Dual-Functional Conjugate of Antigenic Peptide and Fc-III Mimetics (DCAF)
Published on: September 17, 2019
Optimizing TFA Peptide Rink Amide Resin Acidolysis Using Hydrogen Chloride
Marc Gros1, Eudald Asensio-Borràs1, Yolanda Cajal2,3
1Department of Inorganic and Organic Chemistry, University of Barcelona, 08026Barcelona, Spain.
Abstract:
We report an optimization of the standard acidolysis release of peptides from Rink Amide aminomethyl (RA-AM) resin using a combination of trifluoroacetic acid (TFA) and concentrated aqueous hydrogen chloride. The standard TFA-based protocol often leads to incomplete cleavage and reduced peptide yields. Addition of small percentages of HCl to TFA furnishes practically quantitative cleavage yields, improving overall efficiency and reproducibility. Yield improvements between 9 and 52% have been accomplished.
Related Concept Videos
Acid Halides to Carboxylic Acids: Hydrolysis
As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen π bond along with the departure of a halide ion. A final proton transfer step yields carboxylic acid...
Acid Halides to Amides: Aminolysis
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
Preparation of Acid Anhydrides
The carboxylate ion acts as a nucleophile that attacks the carbonyl carbon of the acid chloride to form a tetrahedral intermediate. Subsequently, the re-formation of the carbonyl group with the loss of the chloride ion as a leaving group leads to the formation of an acid...
Amides to Carboxylic Acids: Hydrolysis
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
Acid Halides to Esters: Alcoholysis
Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Overview

