Cinnamosyn, a Cinnamoylated Synthetic-Bioinformatic Natural Product with Cytotoxic Activity

Org Lett. 2024 May 31;26(21):4433-4437. doi: 10.1021/acs.orglett.4c00999. Epub 2024 May 20.

Abstract

Most biosynthetic gene clusters (BGCs) are functionally inaccessible by using fermentation methods. Bioinformatic-coupled total synthesis provides an alternative approach for accessing BGC-encoded bioactivities. To date, synthetic bioinformatic natural product (synBNP) methods have focused on lipopeptides containing simple lipids. Here we increase the bioinformatic and synthetic complexity of the synBNP approach by targeting BGCs that encode N-cinnamoyl lipids. This led to our synthesis of cinnamosyn, a 10-mer N-cinnamoyl-containing peptide that is cytotoxic to human cells.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Biological Products* / chemical synthesis
  • Biological Products* / chemistry
  • Biological Products* / pharmacology
  • Cinnamates / chemical synthesis
  • Cinnamates / chemistry
  • Cinnamates / pharmacology
  • Computational Biology
  • Humans
  • Lipopeptides / chemical synthesis
  • Lipopeptides / chemistry
  • Lipopeptides / pharmacology
  • Molecular Structure
  • Multigene Family

Substances

  • Biological Products
  • Lipopeptides
  • Cinnamates
  • Antineoplastic Agents