Issue 74, 2013
From the journal:

Chemical Communications

Acid-cleavable thiomaleamic acid linker for homogeneous antibody–drug conjugation†

Lourdes Castañeda,a   Antoine Maruani,a   Felix F. Schumacher,a   Enrique Miranda,b   Vijay Chudasama,a   Kerry A. Chester,b   James R. Baker,a   Mark E. B. Smith*a  and  Stephen Caddick*a  

* Corresponding authors

a Department of Chemistry, University College London, 20 Gordon Street, London, UK
E-mail: m.e.b.smith@ucl.ac.uk, vpenterprise@ucl.ac.uk
Tel: +44 (0)20 7679 7538

b UCL Cancer Institute, 72 Huntley Street, London, UK

Abstract

In this communication we describe a novel acid-cleavable linker strategy for antibody–drug conjugation. Functional disulfide bridging of the single interchain disulfide bond of a trastuzumab Fab fragment yields a homogeneous antibody–drug conjugate bearing a thiomaleamic acid linker. This linker is stable at physiological pH and temperature, but quantitatively cleaves at lysosomal pH to release the drug payload.

Graphical abstract: Acid-cleavable thiomaleamic acid linker for homogeneous antibody–drug conjugation

About
Cited by
Related
Download options Please wait...

Supplementary files

Article information

DOI
https://doi.org/10.1039/C3CC45220D
Article type
Communication
Submitted
11 Jul 2013
Accepted
02 Aug 2013
First published
05 Aug 2013
This article is Open Access
Creative Commons BY license

Chem. Commun., 2013,49, 8187-8189

Permissions

Request permissions

Acid-cleavable thiomaleamic acid linker for homogeneous antibody–drug conjugation

L. Castañeda, A. Maruani, F. F. Schumacher, E. Miranda, V. Chudasama, K. A. Chester, J. R. Baker, M. E. B. Smith and S. Caddick, Chem. Commun., 2013, 49, 8187 DOI: 10.1039/C3CC45220D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements