Creative Biolabs provides the unique LACI-D1 scaffold library construction service by the innovative Hi-Affi™ phage display platform. With this powerful platform, our scientists can build high affinity libraries to satisfy customers’ specific requirements.
LACI-D1, is a kind of the Kunitz type scaffold, identified from the first Kunitz domain of human lipoprotein-associated coagulation inhibitor, which is also known astissue factor pathway inhibitor-I (TFPI-I). TFPI is a serum protein consists of three multivalent tandem Kunitz domains, an acidic amino-terminal region and a basic carboxy-terminal end. The first Kunitz domain of TFPI is known to bind to FVIIa and the second binds to and inhibits FXa, while the third Kunitz domain may be related to the association of TFPI with lipoproteins, but the detailed function is still unclear. In general, Kunitz type scaffold can be characterized as small α/β-proteins stabilized by three disulfide bonds and have few secondary structure elements. In addition, they are tight-binding, reversible inhibitors of serine proteases. Therefore, standalone Kunitz domains (e.g. LACI-D1) can be used as a framework for the development of new pharmaceutical drugs.
One successful example of LACI-D1 scaffold is recognized as DX-88 (the investigational name of ecallantide), which has been used for the treatment of hereditary angioedema (HAE) and in the prevention of blood loss in cardiothoracic surgery. As a kind of mimic antibody, DX-88 is selected from LACI-D1 phage display libraries consisting of rationally designed variants to inhibit kallikrein, which is a serine protease activated in many physiological processes such as intrinsic coagulation, fibrinolysis, hypotension and inflammation. In this way, the patients who get insufficient amounts of the natural kallikrein inhibitor C1 could be treated with DX-88, instead of conventional therapy with C1 isolated from human plasma. Currently, Creative Biolabs is pleased to assist our customers to tailor their specific LACI-D1 scaffold libraries and the further screening services for interested targets are available as well.
Scientists from Creative Biolabs have adopted a proprietary phage display based platform known as Hi-Affi™ for our scaffold libraries construction. It is an improved phage display technology combined with the trimer codon technology and NNK method, which can create a large repertoire of variants for specific protein scaffolds. With this powerful platform, our LACI-D1 scaffold libraries can obtain high affinity with 100% precise mutant and over 1010 diversity.
Creative Biolabs promises the timely quotation, high quality service, fast delivery cycle and the most competitive price for each library construction project. With long-term extensive experience in the field of scaffold library construction, our scientists are confident in offering the best service to promote customers’ research project.
Fig. 1 KD1 of human TFPI in complex with a synthetic peptide. (PDB ID: 4BQD)