# A Modular and Convergent “Stick and Click” Conjugation Platform Enables Fast Antibody Conjugate Library Synthesis

**Authors:** Connor Livingstone, Simon Nicolle, Gavin Jones, Craig Jamieson

PMC · DOI: 10.1021/acs.bioconjchem.5c00461 · Bioconjugate Chemistry · 2026-01-07

## TL;DR

This paper introduces a new platform for quickly making antibody drug conjugates by combining different payloads and conjugation methods in a modular way.

## Contribution

A modular and convergent conjugation platform is introduced for efficient and flexible synthesis of antibody conjugate libraries.

## Key findings

- A convergent synthesis approach was used to assemble a library of antibody conjugates with varied payloads and conjugation methods.
- The platform allows for cleavable and noncleavable linker technologies to be integrated seamlessly.
- The method enables direct comparison and targeted optimization of conjugate properties.

## Abstract

The preparation of antibody drug conjugates (ADC) most often relies on a linear sequence to elaborate the small molecule component, followed by a final bioconjugation step to attach it to its immunoglobulin partner. This linear and iterative approach is incompatible with expedient parallel synthesis and process automation. Here, we describe the design and implementation of a general modular platform for the assembly of ADCs that enables facile variation in the nature of the payload, the linker composition, and the type of bioconjugation technique used. A library of antibody conjugates bringing together several different antibodies and payloads was prepared in a convergent fashion using a range of conjugation methods, as well as cleavable or noncleavable linker technology. Aside from offering a direct comparison of different conjugation method performances, this approach enables a more targeted optimization strategy of conjugate properties by deconvoluting bioconjugation and payload attachment.

## Full-text entities

- **Genes:** SLTM (SAFB like transcription modulator) [NCBI Gene 79811] {aka Met}, VHL (von Hippel-Lindau tumor suppressor) [NCBI Gene 7428] {aka HRCA1, RCA1, VHL1, pVHL}, SAFB (scaffold attachment factor B) [NCBI Gene 6294] {aka HAP, HET, SAB-B1, SAF-B, SAF-B1, SAFB1}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, FANCB (FA complementation group B) [NCBI Gene 2187] {aka FA2, FAAP90, FAAP95, FAB, FACB}, SPR (sepiapterin reductase) [NCBI Gene 6697] {aka SDR38C1}, PC (pyruvate carboxylase) [NCBI Gene 5091] {aka PCB}, GADL1 (GAD like acidic amino acid decarboxylase 1) [NCBI Gene 339896] {aka ADC, CSADC, HuADC, HuCSADC}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}
- **Diseases:** solid tumors (MESH:D009369), cytotoxic (MESH:D064420), asthma (MESH:D001249), hematological tumors (MESH:D019337)
- **Chemicals:** acetonitrile (MESH:C032159), Cysteine (MESH:D003545), NHS ester 4 (-), Methionine (MESH:D008715), isopropanol (MESH:D019840), biotin (MESH:D001710), 13C (MESH:C000615229), metal (MESH:D008670), carbamate (MESH:D002219), trifluoroacetic acid (MESH:D014269), SDS (MESH:D012967), Herceptin (MESH:D000068878), Valine (MESH:D014633), N (MESH:D009584), ammonium bicarbonate (MESH:C027043), Kadcyla (MESH:D000080044), lipid (MESH:D008055), triethylamine (MESH:C016162), neopentylamine (MESH:C054458), azide (MESH:D001386), alkyne (MESH:D000480), formic acid (MESH:C030544), Tryptophan (MESH:D014364), phosphoric acid (MESH:C030242), MES (MESH:C004550), TADs (MESH:C406672), Polyacrylamide (MESH:C016679), CO2 (MESH:D002245), DIPEA (MESH:C027070), PBS (MESH:D007854), water (MESH:D014867), citrulline (MESH:D002956), glycan (MESH:D011134), H (MESH:D006859), tetramethylsilane (MESH:C073196), DMSO (MESH:D004121), TCEP (MESH:C080938), Amine (MESH:D000588), Tyrosine (MESH:D014443), VC (MESH:C098534), disulfide (MESH:D004220), lysine (MESH:D008239), Cystine (MESH:D003553), fluorescein (MESH:D019793), phosphine (MESH:C044646)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** Valine-alanine, Valine-alanine 6, C for 16-20
- **Cell lines:** HEK293-6E — Homo sapiens (Human), Transformed cell line (CVCL_HF20)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12863055/full.md

## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12863055/full.md

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Source: https://tomesphere.com/paper/PMC12863055