N-Terminal selective modification of peptides and proteins using 2-ethynylbenzaldehydes

Jie Ren Deng, Nathanael Chun Him Lai, Karen Ka Yan Kung, Bin Yang, Sai Fung Chung, Alan Siu Lun Leung, Man Chung Choi, Yun Chung Leung, Man Kin Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

1 Citation (Scopus)

Abstract

Selective modification of the N-terminus of peptides and proteins is a promising strategy for single site modification methods. Here we report N-terminal selective modification of peptides and proteins by using 2-ethynylbenzaldehydes (2-EBA) for the production of well-defined bioconjugates. After reaction screening with a series of 2-EBA, excellent N-terminal selectivity is achieved by the reaction in slightly acidic phosphate-buffered saline using 2-EBA with electron-donating substituents. Selective modification of a library of peptides XSKFR (X = either one of 20 natural amino acids) by 2-ethynyl-4-hydroxy-5-methoxybenzaldehyde (2d) results in good-to-excellent N-terminal selectivity in peptides (up to >99:1). Lysozyme, ribonuclease A and a therapeutic recombinant Bacillus caldovelox arginase mutant (BCArg mutant) are N-terminally modified using alkyne- and fluorescein-linked 2-EBA. Alkyne-linked BCArg mutant is further modified by rhodamine azide via copper(I)-catalyzed [3 + 2] cycloaddition indicating that the reaction has high functional group compatibility. Moreover, the BCArg mutant modified by 2-ethynyl-5-methoxybenzaldehyde (2b) exhibits comparable activity in enzymatic and cytotoxic assays with the unmodified one.

Original languageEnglish
Article number67
JournalCommunications Chemistry
Volume3
Issue number1
DOIs
Publication statusE-pub ahead of print - 29 May 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Chemistry
  • Environmental Chemistry
  • Biochemistry

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