Structural highlights
7neu is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , , |
| Gene: | CPB2 (HUMAN) |
| Activity: | Carboxypeptidase U, with EC number 3.4.17.20 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[CBPB2_HUMAN] Cleaves C-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Down-regulates fibrinolysis by removing C-terminal lysine residues from fibrin that has already been partially degraded by plasmin.[1]
Publication Abstract from PubMed
Selective and potent inhibitors of activated thrombin activatable fibrinolysis inhibitor (TAFIa) have the potential to increase endogenous and therapeutic fibrinolysis and to behave like profibrinolytic agents without the risk of major hemorrhage, since they do not interfere either with platelet activation or with coagulation during blood hemostasis. Therefore, TAFIa inhibitors could be used in at-risk patients for the treatment, prevention, and secondary prevention of stroke, venous thrombosis, and pulmonary embolisms. In this paper, we describe the design, the structure-activity relationship (SAR), and the synthesis of novel, potent, and selective phosphinanes and azaphosphinanes as TAFIa inhibitors. Several highly active azaphosphinanes display attractive properties suitable for further in vivo efficacy studies in thrombosis models.
Phosphinanes and Azaphosphinanes as Potent and Selective Inhibitors of Activated Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa).,Schaffner AP, Sansilvestri-Morel P, Despaux N, Ruano E, Persigand T, Rupin A, Mennecier P, Vallez MO, Raimbaud E, Desos P, Gloanec P J Med Chem. 2021 Mar 25. doi: 10.1021/acs.jmedchem.0c02072. PMID:33764059[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mao SS, Cooper CM, Wood T, Shafer JA, Gardell SJ. Characterization of plasmin-mediated activation of plasma procarboxypeptidase B. Modulation by glycosaminoglycans. J Biol Chem. 1999 Dec 3;274(49):35046-52. PMID:10574983
- ↑ Schaffner AP, Sansilvestri-Morel P, Despaux N, Ruano E, Persigand T, Rupin A, Mennecier P, Vallez MO, Raimbaud E, Desos P, Gloanec P. Phosphinanes and Azaphosphinanes as Potent and Selective Inhibitors of Activated Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa). J Med Chem. 2021 Mar 25. doi: 10.1021/acs.jmedchem.0c02072. PMID:33764059 doi:http://dx.doi.org/10.1021/acs.jmedchem.0c02072
