# Tetrapeptide GGFG (maleimide-GGFG-aminomethyl)

Source: https://onco.cc/terms/ggfg/  
OnCo record `ggfg` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The GGFG tetrapeptide (glycine-glycine-phenylalanine-glycine) is the tether between antibody and payload in Enhertu and Dato-DXd. Lysosomal cathepsins cut it inside the cancer cell, and it holds in circulation well enough to allow eight payloads per antibody, a load earlier linkers could not carry safely.

## Summary

The glycine-glycine-phenylalanine-glycine tetrapeptide is cleaved by lysosomal cathepsins, releasing DXd through a self-immolative aminomethylene spacer. Its stability in circulation allows a drug-to-antibody ratio of eight with acceptable off-target exposure, a combination that earlier linkers could not deliver.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: tetrapeptide linker; GGFG-DXd

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Trastuzumab_deruxtecan
- DS-8201a with GGFG-DXd linker-payload (Ogitani et al., Clin Cancer Res 2016): https://doi.org/10.1158/1078-0432.CCR-15-2822

## Connected records

- terms: [DXd](https://onco.cc/terms/dxd/), [Linker (ADC)](https://onco.cc/terms/linker/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- drugs: [Datopotamab deruxtecan](https://onco.cc/drugs/datopotamab-deruxtecan/), [Ifinatamab deruxtecan](https://onco.cc/drugs/ifinatamab-deruxtecan/), [Patritumab deruxtecan](https://onco.cc/drugs/patritumab-deruxtecan/), [Raludotatug deruxtecan](https://onco.cc/drugs/raludotatug-deruxtecan/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- key papers: [DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1](https://onco.cc/key-papers/paper-ogitani-clin-cancer-res/)

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