Engineered Multivalent FGF1 Probe Targets HSPGs With Potential Antiviral Activity

Researchers have engineered a multivalent, self-assembling molecular probe based on fibroblast growth factor-1 that demonstrates a defined architecture, preserved structural stability, and markedly improved interaction with targets containing heparan sulfate proteoglycans. Developed as a tetrameric biosensor complex, the construct utilizes an engineered protein scaffold to assemble an FGF1 mutant deficient in native receptor binding.

Data reported from the study suggest that this multivalent biosensor derived from fibroblast growth factor-1 has the capacity to block the binding of endogenous growth factors and viral proteins to cell-surface heparan sulfate proteoglycans. The multivalent assembly presents potential antiviral activity alongside its diagnostic utility.

To produce the probe, the investigators harnessed the natural heparan sulfate recognition properties of fibroblast growth factor-1 through controlled oligomerization. The team utilized an engineered streptavidin platform to assemble a tetrameric complex incorporating a specific fibroblast growth factor-1 mutant designed with enhanced heparan sulfate affinity and a deficiency in binding fibroblast growth factor receptors.

Heparan sulfate proteoglycans are sulfated glycoconjugates that are broadly distributed across the plasma membrane and throughout the surrounding extracellular matrix. Through physical interactions mediated by their heparan sulfate chains, these molecules participate directly in multiple cellular mechanisms, including the internalization of extracellular ligands and the regulation of key cellular signaling pathways.

Pathological remodeling and aberrant abundance of heparan sulfate proteoglycans have been established in several disease states, most notably during malignant transformation. Because these alterations are closely linked with disease progression, cell-surface proteoglycans represent attractive molecular targets for both diagnostic biosensing and targeted therapeutic intervention.

Under normal physiological conditions, endogenous fibroblast growth factors associate simultaneously with heparan sulfate proteoglycans and fibroblast growth factor receptors to initiate downstream cellular signaling cascades. By uncoupling heparan sulfate binding from receptor activation within a stable tetrameric structure, the brief report documented in Cell Communication and Signaling demonstrates an engineered approach to selectively probe and intercept proteoglycan-mediated interactions.

Subject of Research: Engineered multivalent protein probes targeting heparan sulfate proteoglycans

Article Title: Multivalent self-assembling fibroblast growth factor-1-based molecular probe with high affinity for HSPGs and potential antiviral activity

Article References: Chorążewska, A., Ciura, K., Pomorski, A., Porębska, N., & Opaliński, Ł. (2026). Multivalent self-assembling fibroblast growth factor-1-based molecular probe with high affinity for HSPGs and potential antiviral activity. Cell Communication and Signaling. https://doi.org/10.1186/s12964-026-03307-y

Image Credits: AI Generated

DOI: 10.1186/s12964-026-03307-y

Keywords: Fibroblast Growth Factor 1, Heparan Sulfate Proteoglycans, Molecular Probes, Streptavidin Platform, Antiviral Research, Biosensors, Glycoconjugates, Cell Signaling, Multivalent, self-assembling, fibroblast, growth