D'Alessandro, Pier Luca, Hollingworth, Greg and Vorherr, Thomas (2019) Real-time imaging and quantification of peptide uptake in vitro and in vivo. ACS Chemical Biology. ISSN 1554-89291554-8937

Abstract

Peptides constitute an important class of molecules for drug discovery, but many of the leads fail to advance clinically because of poor membrane and tissue permeability. Therefore, assessment of a peptide’s ability to cross cellular membrane is critical when developing novel peptide-based therapeutics. However, current methods suffer from limitations such as the necessity to introduce rather large modifications that require complex chemistry, the inability to provide kinetic information of internalization or distinguish between internalized vs membrane bound compounds, as well as requiring multiple sample manipulation steps. Herein, we report a novel “Split Luciferin Peptide” (SLP) uptake assay that provides non-invasive imaging and quantification of peptide uptake in real-time both in vitro and in vivo using a very sensitive bioluminescent readout. The method is based on a straightforward chemical modification of the peptide of interest with a D-cysteine tag retains the overall peptidic character of the original molecule. This method can in principle be adapted for screening of peptide libraries becoming an important tool for preclinical drug development both in vitro and in vivo.

Item Type:	Article
Keywords:	Bioluminescence, peptides, p53, mdm2
Date Deposited:	25 Sep 2019 00:45
Last Modified:	25 Sep 2019 00:45
URI:	https://oak.novartis.com/id/eprint/38975