Biochemical and Functional Characterization of LIZ, a Marine-Derived Serine Protease That Degrades Cross-Linked Fibrin and Attenuates Experimental Thrombosis.
- 1Department of Biomedical Science, College of Natural Sciences, Chosun University, Jeonnam-Gwangju Integrated Special City 61452, Republic of Korea.
- 2Department of Integrative Biological Science & BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun University, Jeonnam-Gwangju Integrated Special City 61452, Republic of Korea.
Abstract
Background/Objectives: Direct fibrin-degrading proteases may provide a mechanistically distinct approach to clot proteolysis, but their development requires definition of catalytic behavior, fibrin selectivity, molecular identity, and safety. We characterized an activity-containing preparation from the marine polychaete Lepidasthenia izukai, designated LIZ. Methods: LIZ was obtained by ammonium sulfate fractionation and sequential chromatography. N-terminal sequencing, inhibitor profiling, chromogenic-substrate screening and S-2288 kinetics, fibrinogenolysis, direct fibrin-degradation assays, a κ-carrageenan rat-tail thrombosis model, and cell viability were evaluated. Results: The final preparation showed a predominant band at approximately 28 kDa. N-terminal sequencing yielded IMGGSEAS, providing sequence-level characterization without definitive molecular identification. PMSF abolished activity and DFP reduced it to 9.8%, supporting a serine-protease biochemical profile. For S-2288, Km was 0.029 ± 0.003 mM and apparent kcat/Km was 39.7 ± 4.3 mM⁻¹ s⁻¹. LIZ degraded fibrinogen Aα within 30 s and Bβ and γ within 20 min, decreased pre-formed fibrin-polymer turbidity, and degraded FXIIIa-cross-linked fibrin. In the pretreatment model, thrombotic tail length was 0.7 ± 1.0% with LIZ, 86.1 ± 3.2% with κ-carrageenan alone, and 0.5 ± 0.6% with uPA (n = 3/group). Conclusions: LIZ shows direct activity against structurally stabilized fibrin and proof-of-concept antithrombotic activity. However, the data do not establish definitive molecular identity, therapeutic thrombolysis, fibrin selectivity, relative potency, or a therapeutic safety window. Further molecular, pharmacological, and safety studies are required.
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BibTeX
@article{yun2026biochemical,
title = {{Biochemical and Functional Characterization of LIZ, a Marine-Derived Serine Protease That Degrades Cross-Linked Fibrin and Attenuates Experimental Thrombosis.}},
author = {Sang-Gu Yun and Jung Eun Park},
journal = {Pharmaceutics},
year = {2026},
month = oct,
doi = {10.3390/pharmaceutics18101294},
url = {https://europepmc.org/article/MED/42942825},
note = {CC BY},
}
RIS
TY - JOUR
TI - Biochemical and Functional Characterization of LIZ, a Marine-Derived Serine Protease That Degrades Cross-Linked Fibrin and Attenuates Experimental Thrombosis.
AU - Sang-Gu Yun
AU - Jung Eun Park
PY - 2026
DA - 2026/10/12
JO - Pharmaceutics
DO - 10.3390/pharmaceutics18101294
UR - https://europepmc.org/article/MED/42942825
AB - Background/Objectives: Direct fibrin-degrading proteases may provide a mechanistically distinct approach to clot proteolysis, but their development requires definition of catalytic behavior, fibrin selectivity, molecular identity, and safety. We characterized an activity-containing preparation from the marine polychaete Lepidasthenia izukai, designated LIZ. Methods: LIZ was obtained by ammonium sulfate fractionation and sequential chromatography. N-terminal sequencing, inhibitor profiling, chromogenic-substrate screening and S-2288 kinetics, fibrinogenolysis, direct fibrin-degradation assays, a κ-carrageenan rat-tail thrombosis model, and cell viability were evaluated. Results: The final preparation showed a predominant band at approximately 28 kDa. N-terminal sequencing yielded IMGGSEAS, providing sequence-level characterization without definitive molecular identification. PMSF abolished activity and DFP reduced it to 9.8%, supporting a serine-protease biochemical profile. For S-2288, Km was 0.029 ± 0.003 mM and apparent kcat/Km was 39.7 ± 4.3 mM⁻¹ s⁻¹. LIZ degraded fibrinogen Aα within 30 s and Bβ and γ within 20 min, decreased pre-formed fibrin-polymer turbidity, and degraded FXIIIa-cross-linked fibrin. In the pretreatment model, thrombotic tail length was 0.7 ± 1.0% with LIZ, 86.1 ± 3.2% with κ-carrageenan alone, and 0.5 ± 0.6% with uPA (n = 3/group). Conclusions: LIZ shows direct activity against structurally stabilized fibrin and proof-of-concept antithrombotic activity. However, the data do not establish definitive molecular identity, therapeutic thrombolysis, fibrin selectivity, relative potency, or a therapeutic safety window. Further molecular, pharmacological, and safety studies are required.
SN - 1999-4923
ER -