Related Experiment Video
Updated: Jun 13, 2025

Targeted Antibody Blocking by a Dual-Functional Conjugate of Antigenic Peptide and Fc-III Mimetics DCAF
Published on: September 17, 2019
Introducing Chemoselective Peptide Conjugation via N-Alkylation of Pyridyl-alanine: Solution and Solid Phase
Soumit Dutta1, Arnab Chowdhury1, Anupam Bandyopadhyay1
1Biomimetic Peptide Engineering Lab, Department of Chemistry, Indian Institute of Technology Ropar, Birla Farms, Rupnagar, Punjab 140001, India.
Abstract:
A novel chemoselective peptide conjugation via late-stage N-alkylation of pyridyl-alanine (PAL) in the solution and solid phase, namely, NAP, is demonstrated. The method constructs functionally diverse and highly stable N-alkylated conjugates with various peptides. Notably, conjugations in the solid phase offered a more economical process. The method can provide the opportunity for dual labeling along with a cysteine handle in a peptide chain. Finally, we showcased that the antiproliferative activities of the p53 peptide (MDM2 inhibitor) could be 2-fold enhanced via NAP conjugation with the RGD peptide (selective integrin binder).
Related Concept Videos
Phase II Reactions: Sulfation and Conjugation with α-Amino Acids
Amines to Amides: Acylation of Amines
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
Preparation of Amines: Alkylation of Ammonia and Amines
Each alkylation step makes the nitrogen center more nucleophilic, which triggers successive alkylations until a quaternary ammonium salt is formed. Considering...
Preparation of 1° Amines: Azide Synthesis
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...
Preparation of 1° Amines: Gabriel Synthesis
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Preparation of Alkynes: Alkylation Reaction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.

