Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Preparation of 1° Amines: Azide Synthesis01:22

Preparation of 1° Amines: Azide Synthesis

4.2K
Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
4.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Azapeptide Atropisomers From Late-Stage <i>N</i>-Alkylations.

The Journal of organic chemistry·2025
Same author

Oxidative Couplings of <i>N</i>-Aryl Peptides in Organic Solvent: Preventing Amino Acid Side Chain Loss.

Organic letters·2025
Same author

Metallo-azapeptides: Controlled Metal Chelation to Peptide Backbone Nitrogen.

Journal of the American Chemical Society·2025
Same author

Peptoid-based macrodiscs of variable lipid composition for structural studies of membrane proteins by oriented-sample solid-state NMR.

Journal of structural biology: X·2023
Same author

Late-Stage Chloride Displacements Enable Access to Peptoids with <i>cis</i>-Inducing Alkylammonium Side Chains.

Organic letters·2023
Same author

Correction to "Late-Stage <i>N</i>-Alkylation of Azapeptides".

Organic letters·2023

Related Experiment Video

Updated: Oct 26, 2025

Solid-phase Submonomer Synthesis of Peptoid Polymers and their Self-Assembly into Highly-Ordered Nanosheets
13:42

Solid-phase Submonomer Synthesis of Peptoid Polymers and their Self-Assembly into Highly-Ordered Nanosheets

Published on: November 2, 2011

29.7K

Solid phase submonomer azapeptide synthesis.

Maxwell Bowles1, Caroline Proulx1

  • 1Department of Chemistry, North Carolina State University, Raleigh, NC, United States.

Methods in Enzymology
|July 30, 2021
PubMed
Summary

This study details a solid-phase submonomer synthesis for azapeptides, featuring a novel three-step protocol. This method efficiently creates diverse peptidomimetics with various side chains on solid support.

Keywords:
Aza-amino acidsAzapeptidesPeptidomimeticsSemicarbazideSemicarbazoneSolid phase peptide synthesisSubmonomer

More Related Videos

An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity
12:02

An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity

Published on: November 2, 2016

12.3K
Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly
09:34

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly

Published on: February 6, 2020

7.5K

Related Experiment Videos

Last Updated: Oct 26, 2025

Solid-phase Submonomer Synthesis of Peptoid Polymers and their Self-Assembly into Highly-Ordered Nanosheets
13:42

Solid-phase Submonomer Synthesis of Peptoid Polymers and their Self-Assembly into Highly-Ordered Nanosheets

Published on: November 2, 2011

29.7K
An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity
12:02

An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity

Published on: November 2, 2016

12.3K
Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly
09:34

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly

Published on: February 6, 2020

7.5K

Area of Science:

  • Peptide Chemistry
  • Organic Synthesis
  • Medicinal Chemistry

Background:

  • Azapeptides, incorporating aza-amino acids with a nitrogen atom replacing the α-carbon, are valuable in medicinal chemistry and biomaterials.
  • Solid-phase synthesis is a cornerstone for constructing peptides and peptidomimetics.

Purpose of the Study:

  • To present a detailed step-by-step protocol for the solid-phase submonomer synthesis of azapeptides.
  • To enable the rapid and diverse synthesis of peptidomimetics with varied side chains.

Main Methods:

  • Solid-phase submonomer synthesis protocol involving three key steps.
  • Step 1: Hydrazone activation and coupling to a resin-bound peptide.
  • Step 2: Chemoselective semicarbazone functionalization for aza-amino acid side chain installation via N-alkylation with primary alkyl halides.
  • Step 3: Orthogonal deprotection of the semicarbazone to complete the monomer addition cycle.

Main Results:

  • Successful demonstration of a three-step solid-phase submonomer synthesis for azapeptides.
  • Efficient installation of aza-amino acid side chains through chemoselective semicarbazone functionalization.
  • Facilitation of rapid introduction of diverse natural and unnatural side chains onto solid support.

Conclusions:

  • The described protocol accelerates the synthesis of azapeptides and related peptidomimetics.
  • This method allows for the versatile incorporation of various side chains using accessible submonomers.
  • The approach is applicable for creating novel compounds in medicinal chemistry and biomaterials development.