publications

2024

1. Gold III Induced Amide Bond Cleavage In Vivo. A Dual Release Strategy via pi-acid Catalysed Allyl Substitution

   V. B. Unnikrishnan, V. Sabatino, F. Amorim, and 5 more authors

   Journal of the American Chemical Society 2024

   Abs Bib HTML

   Selective cleavage of amide bonds holds prominent significance by facilitating precise manipulation of biomolecules, with implications spanning from basic research to therapeutic interventions. However, achieving selective cleavage of amide bonds via mild synthetic chemistry routes poses a critical challenge. Here, we report a novel amide bond-cleavage reaction triggered by Na[AuCl4] in mild aqueous conditions, where a crucial cyclization step leads to the formation of a 5-membered ring intermediate that rapidly hydrolyses to release the free amine in high yields. Notably, the reaction exhibits remarkable site-specificity to cleave peptide bonds at the C-terminus of allyl-glycine. The strategic introduction of a leaving group at the allyl position facilitated a dual-release approach through π-acid catalyzed substitution. This reaction was employed for the targeted release of the cytotoxic drug monomethyl auristatin E in combination with an antibody-drug conjugate in cancer cells. Finally, Au-mediated prodrug activation was shown in a colorectal zebrafish xenograft model, leading to a significant increase in apoptosis and tumor shrinkage. Our findings reveal a novel metal-based cleavable reaction expanding the utility of Au complexes beyond catalysis to encompass bond-cleavage reactions for cancer therapy.

   @article{unnikrishnan2024gold,
     title = {Gold III Induced Amide Bond Cleavage In Vivo. A Dual Release Strategy via pi-acid Catalysed Allyl Substitution},
     volume = {146},
     issn = {0021-9606},
     url = {https://doi.org/10.1021/jacs.4c05582},
     doi = {10.1021/jacs.4c05582},
     number = {12},
     journal = {Journal of the American Chemical Society},
     author = {Unnikrishnan, V. B. and Sabatino, V. and Amorim, F. and Estrada, M. F. and Navo, C. D. and Jimenez-Oses, G. and Fior, R. and Bernardes, G. J. L.},
     year = {2024},
     pages = {23240--23252},
     csp = {true}
   }

2023

1. Disintegration theory enabling precision engineering of proteins

   P. Chauhan, V. Ragendu, M. Kumar, and 3 more authors

   ACS Central Science 2023

2022

1. Transition-metal-mediated bioorthogonal release

   V. Sabatino, V. B. Unnikrishnan, and G. J. L. Bernardes

   Chemical Catalysis 2022

2020

1. Single amino-acid Gly-tag enables metal-free protein purification

   L. Purushottam*, V. B. Unnikrishnan*, M. Gujrati, and 4 more authors

   Chemical Science 2020
2. Platinum-triggered bond cleavage of pentynoyl amide and \emphN-propargyl handles for drug activation in vivo

   B. L. Oliveira, B. J. Stenton, V. B. Unnikrishnan, and 8 more authors

   Journal of the American Chemical Society 2020

2019

1. Single-site glycine-specific labelling of proteins

   L. Purushottam, S. Adusumalli, U. Singh, and 5 more authors

   Nature Communications 2019