Balancing Reactivity and Specificity: Fc-Binding O-Acyl Hydroxamate Reagents for Site-Selective Antibody Labeling at Lys248

Jin Woo Seo; Sun Hee Park; Jinyoung Kim; Tae Jin Lee; Seong Hyun Park; Ju Hwan Kim; Taedong Han; Sang J. Chung

doi:10.1021/acs.orglett.5c01424

Balancing Reactivity and Specificity: Fc-Binding O-Acyl Hydroxamate Reagents for Site-Selective Antibody Labeling at Lys248

Jin Woo Seo, Sun Hee Park, Jinyoung Kim, Tae Jin Lee, Seong Hyun Park, Ju Hwan Kim, Taedong Han, Sang J. Chung

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

Abstract

We report the design and synthesis of O-acyl hydroxamates (OAHs) affinity labels for selective modification of human IgG1 at Lys248 via proximity-driven acylation. Optimized compound 7g exhibits high water stability and >99% site-selective conversion at Lys248 on Trastuzumab using only 3 equiv. Peptide mapping and fluorescence labeling confirm its precision, establishing 7g as a robust platform for efficient and site-selective antibody conjugation.

Original language	English
Pages (from-to)	5665-5668
Number of pages	4
Journal	Organic Letters
Volume	27
Issue number	22
DOIs	https://doi.org/10.1021/acs.orglett.5c01424
State	Published - 6 Jun 2025

Access to Document

10.1021/acs.orglett.5c01424

Cite this

@article{c97734a95502439782d0deaa86a647f5,

title = "Balancing Reactivity and Specificity: Fc-Binding O-Acyl Hydroxamate Reagents for Site-Selective Antibody Labeling at Lys248",

abstract = "We report the design and synthesis of O-acyl hydroxamates (OAHs) affinity labels for selective modification of human IgG1 at Lys248 via proximity-driven acylation. Optimized compound 7g exhibits high water stability and >99\% site-selective conversion at Lys248 on Trastuzumab using only 3 equiv. Peptide mapping and fluorescence labeling confirm its precision, establishing 7g as a robust platform for efficient and site-selective antibody conjugation.",

author = "Seo, \{Jin Woo\} and Park, \{Sun Hee\} and Jinyoung Kim and Lee, \{Tae Jin\} and Park, \{Seong Hyun\} and Kim, \{Ju Hwan\} and Taedong Han and Chung, \{Sang J.\}",

note = "Publisher Copyright: {\textcopyright} 2025 American Chemical Society.",

year = "2025",

month = jun,

day = "6",

doi = "10.1021/acs.orglett.5c01424",

language = "English",

volume = "27",

pages = "5665--5668",

journal = "Organic Letters",

issn = "1523-7060",

publisher = "American Chemical Society",

number = "22",

}

TY - JOUR

T1 - Balancing Reactivity and Specificity

T2 - Fc-Binding O-Acyl Hydroxamate Reagents for Site-Selective Antibody Labeling at Lys248

AU - Seo, Jin Woo

AU - Park, Sun Hee

AU - Kim, Jinyoung

AU - Lee, Tae Jin

AU - Park, Seong Hyun

AU - Kim, Ju Hwan

AU - Han, Taedong

AU - Chung, Sang J.

PY - 2025/6/6

Y1 - 2025/6/6

N2 - We report the design and synthesis of O-acyl hydroxamates (OAHs) affinity labels for selective modification of human IgG1 at Lys248 via proximity-driven acylation. Optimized compound 7g exhibits high water stability and >99% site-selective conversion at Lys248 on Trastuzumab using only 3 equiv. Peptide mapping and fluorescence labeling confirm its precision, establishing 7g as a robust platform for efficient and site-selective antibody conjugation.

AB - We report the design and synthesis of O-acyl hydroxamates (OAHs) affinity labels for selective modification of human IgG1 at Lys248 via proximity-driven acylation. Optimized compound 7g exhibits high water stability and >99% site-selective conversion at Lys248 on Trastuzumab using only 3 equiv. Peptide mapping and fluorescence labeling confirm its precision, establishing 7g as a robust platform for efficient and site-selective antibody conjugation.

UR - https://www.scopus.com/pages/publications/105006698474

U2 - 10.1021/acs.orglett.5c01424

DO - 10.1021/acs.orglett.5c01424

M3 - Article

C2 - 40423997

AN - SCOPUS:105006698474

SN - 1523-7060

VL - 27

SP - 5665

EP - 5668

JO - Organic Letters

JF - Organic Letters

IS - 22

ER -

Balancing Reactivity and Specificity: Fc-Binding O-Acyl Hydroxamate Reagents for Site-Selective Antibody Labeling at Lys248

Abstract

Access to Document

Other files and links

Fingerprint

Cite this