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Peptide Bonds

Peptide Bonds

A peptide bond covalently attaches amino acids through a dehydration reaction. One amino acid's carboxyl group and another amino acid's amino group combine, releasing a water molecule. The resulting bond is the peptide bond. The products that such linkages form are peptides. As more amino acids join this growing chain, the resulting chain is a polypeptide. Each polypeptide has a free amino group at one end. This end has the N-terminal, or the amino-terminal, and the other end has a free...

Amides to Carboxylic Acids: Hydrolysis

Amides to Carboxylic Acids: Hydrolysis

Amides can undergo either acid-catalyzed hydrolysis or base-promoted hydrolysis through a typical nucleophilic acyl substitution. Each hydrolysis requires severe conditions.
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 Amides: Aminolysis

Acid Halides to Amides: Aminolysis

Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
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...

Amines to Amides: Acylation of Amines

Amines to Amides: Acylation of Amines

Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...

Preparation of Amides

Preparation of Amides

Amides are synthesized by treating carboxylic acids with amines in the presence of dehydrating agents like dicyclohexylcarbodiimide (DCC).
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...

Translocation of Proteins into the Mitochondria

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...

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Related Experiment Video

Updated: May 30, 2025

Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation

Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation

Published on: August 1, 2018

Peptide Backbone Cleavage and Transamidation via Thioester-to-Imide Acyl Transfer.

Bengt H Gless¹, Sabrina H Schmied¹, Christian A Olsen¹

¹Center for Biopharmaceuticals and Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 160, DK-2100, Copenhagen, Denmark.

|January 31, 2025

Summary

Cysteine thioesters unexpectedly fragment via transamidation, cleaving peptide backbones. This reaction, dependent on sequence and post-translational modifications, reveals new insights into protein reactivity.

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Last Updated: May 30, 2025

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Published on: June 20, 2014

Area of Science:

Biochemistry
Chemical Biology
Proteomics

Background:

Cysteine thioesters are crucial in biological processes.
Their reactivity is well-documented, but new reactions continue to be discovered.

Purpose of the Study:

To investigate the reactivity of S-acylcysteine-containing peptides.
To uncover novel chemical transformations involving cysteine thioesters.

Main Methods:

Synthesis of S-acylcysteine-containing peptides.
Characterization of peptide fragmentation using mass spectrometry and NMR.
Mechanistic studies under varying pH conditions.

Main Results:

Discovered spontaneous peptide backbone cleavage of S-acylcysteine peptides at pH 8-10.
Identified a reversible thioester-to-imide acyl transfer mechanism.
Demonstrated sequence-dependence and occurrence in peptides with post-translational modifications (PTMs) like S-acetylation and S-palmitoylation.

Conclusions:

The transamidation reaction of cysteine thioesters leads to unexpected peptide cleavage.
This reactivity is relevant for understanding protein behavior and PTMs.
Potential for developing new mild peptide and protein modification methods.