1
Return

Bioorthogonal Heptose Phosphate Probes for Chemical Profiling of Bacterial Glycans

delete2026-06-12
delete0
delete
OA
AI
W
Wei Cao
W
Wenkai Liu
M
Ming Yang
L
Luyao Yu
T
Ting Li
Y
Yao Zhou
X
Xiaocui Zheng
L
Li Yi
H
Han Wang
L
Leyi Li
C
Chang Xu
Y
Yi Hsu
J
Jiaming Jin
S
Senlian Hong *
Y
Yixuan Xie *
W
Wei Wang *
J
Jiajia Wang *
谢然 (Ran Xie) *
DOI:10.1021/jacsau.6c00391delete
deleteOriginal
deleteOriginal request for help
deleteShare
deleteSave
Abstract

Abstract

En 中文
Heptose sugars are essential components of Gram-negative bacterial lipopolysaccharide (LPS) and play emerging roles in innate immune activation. To enable functional studies of heptose biology, we developed a bioorthogonal metabolic probe, 7-azido-heptose-1-phosphate (7AzHep1P), which incorporates into the LPS inner core and generates a truncated yet detectable LPS structure. Using click chemistry, we visualized LPS remodeling in live bacteria and confirmed reporter incorporation across various LPS mutants. Notably, 7AzHep1P-labeled LPS preserved immunogenic activity, triggering cytokine release and macrophage activation. We further applied this probe for chemical glycoproteomics, identifying 133 O-heptosylated glycopeptides from 97 bacterial proteins. Beyond canonical serine and threonine sites, heptosylation was also detected on other residues, revealing unappreciated substrate diversity. Together, this strategy enables nongenetic, in situ profiling of heptose-linked biomolecules, offering a valuable tool for dissecting LPS biosynthesis, immune modulation, and glycosylation in bacterial systems.
Keywords:
Bacteria
Fluorescence
Labeling
Peptides and proteins
Probes
heptose
metabolic oligosaccharide engineering
LPS assembly
immunogenic activity
chemical glycoproteomics

Journal

JACS Au cover
JACS Au
IF:
8.7
Papers:
2.3K
Citations:
8.0K

Organization

F
fudan university
Scholars:
11.3W
Papers: 7.6W
Citations: 121
N
nanjing university
Scholars:
7.6W
Papers: 5.5W
Citations: 87
H
henan university
Scholars:
2.2W
Papers: 1.3W
Citations: 20
Cited Papers

Cited Papers

Citing Papers

Citing Papers