A Platform for SpyCatcher Conjugation to Native Antibodies

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F25%3A73632438" target="_blank" >RIV/61989592:15310/25:73632438 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlepdf/2025/sc/d5sc02286j" target="_blank" >https://pubs.rsc.org/en/content/articlepdf/2025/sc/d5sc02286j</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/D5SC02286J" target="_blank" >10.1039/D5SC02286J</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A Platform for SpyCatcher Conjugation to Native Antibodies

Popis výsledku v původním jazyce

Protein–antibody conjugates represent major advancements in targeted therapeutics. However, platforms enabling ‘off-the-shelf’ antibody conjugation are seldom reported. The SpyTag/SpyCatcher system, known for its stable isopeptide bond formation, is widely used to engineer protein architectures and study protein folding. This work introduces the fusion of SpyCatcher with native antibodies using cysteine-reactive tetra-divinylpyrimidine (TetraDVP)-SpyTag linkers. This platform allows for the rapid and stable conjugation of a native antibody with SpyCatcher proteins. As a proof of concept, the HER2-targeting antibody trastuzumab was conjugated to different SpyCatcher proteins using a TetraDVP-SpyTag linker, producing robust conjugates that retained specific binding to HER2-positive cells with excellent conversion rates. To demonstrate the platform’s broader applicability, the TetraDVP-SpyTag linker was successfully conjugated to additional native IgG1 and IgG4 antibodies (durvalumab, brentuximab, cetuximab, and gemtuzumab) with similarly high efficiency as trastuzumab. Moreover, a scalable solid-phase synthesis of TetraDVP linkers has been developed, achieving high yields and purity. This innovative platform enables precise, single-step antibody bioconjugation, offering strong potential for protein–antibody conjugate synthesis. With applications across therapeutics and diagnostics, this method advances antibody-based drug development.

Název v anglickém jazyce

A Platform for SpyCatcher Conjugation to Native Antibodies

Popis výsledku anglicky

Protein–antibody conjugates represent major advancements in targeted therapeutics. However, platforms enabling ‘off-the-shelf’ antibody conjugation are seldom reported. The SpyTag/SpyCatcher system, known for its stable isopeptide bond formation, is widely used to engineer protein architectures and study protein folding. This work introduces the fusion of SpyCatcher with native antibodies using cysteine-reactive tetra-divinylpyrimidine (TetraDVP)-SpyTag linkers. This platform allows for the rapid and stable conjugation of a native antibody with SpyCatcher proteins. As a proof of concept, the HER2-targeting antibody trastuzumab was conjugated to different SpyCatcher proteins using a TetraDVP-SpyTag linker, producing robust conjugates that retained specific binding to HER2-positive cells with excellent conversion rates. To demonstrate the platform’s broader applicability, the TetraDVP-SpyTag linker was successfully conjugated to additional native IgG1 and IgG4 antibodies (durvalumab, brentuximab, cetuximab, and gemtuzumab) with similarly high efficiency as trastuzumab. Moreover, a scalable solid-phase synthesis of TetraDVP linkers has been developed, achieving high yields and purity. This innovative platform enables precise, single-step antibody bioconjugation, offering strong potential for protein–antibody conjugate synthesis. With applications across therapeutics and diagnostics, this method advances antibody-based drug development.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GN22-07138O" target="_blank" >GN22-07138O: Konformačně zamčené konjugáty peptidů a léčiv jako platforma pro cílená terapeutika</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemical Science

ISSN

2041-6520

e-ISSN

2041-6539

Svazek periodika

16

Číslo periodika v rámci svazku

23

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

10602-10609

Kód UT WoS článku

001488356500001

EID výsledku v databázi Scopus

2-s2.0-105005433532