Solid-Phase Synthesis of Caged Luminescent Peptides via Side Chain Anchoring

Bioconjug Chem. 2023 Dec 20;34(12):2234-2242. doi: 10.1021/acs.bioconjchem.3c00381. Epub 2023 Dec 6.

Abstract

The synthesis of caged luminescent peptide substrates remains challenging, especially when libraries of the substrates are required. Most currently available synthetic methods rely on a solution-phase approach, which is less suited for parallel synthesis purposes. We herein present a solid-phase peptide synthesis (SPPS) method for the synthesis of caged aminoluciferin peptides via side chain anchoring of the P1 residue. After the synthesis of a preliminary test library consisting of 40 compounds, the synthetic method was validated and optimized for up to >100 g of resin. Subsequently, two separate larger peptide libraries were synthesized either having a P1 = lysine or arginine residue containing in total 719 novel peptide substrates. The use of a more stable caged nitrile precursor instead of caged aminoluciferin rendered our parallel synthetic approach completely suitable for SPPS and serine protease profiling was demonstrated using late-stage aminoluciferin generation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine
  • Lysine / chemistry
  • Peptide Library
  • Peptides* / chemistry
  • Solid-Phase Synthesis Techniques*

Substances

  • Peptides
  • Peptide Library
  • Lysine
  • Arginine