Creative Biolabs provides the LDTI library construction service with high quality and efficiency using our proprietary Hi-Affi™ platform. Our scientists are confident in generating scaffold libraries with desired diversity and high affinity for potential targets selection, which can be used for drug discovery, development of diagnostic kits and other R&D applications.
The leech-derived tryptase inhibitor (LDTI), a Kazal-type serine proteinase inhibitor is found from the medicinal leech Hirudo medicinalis. As a group of the most versatile proteolytic enzymes, serine proteinases, together with their inhibitors, regulate various physiological and physio-pathological processes, such as blood coagulation, fibrinolysis, complement system, inflammation, and cancer. LDTI is the first described human mast cell tryptase protein inhibitor, and has been purified and produced through recombinant DNA methods. It consists of contains 46 amino acid residues and structurally similar to bdellin B-3, a plasmin and trypsin inhibitor, and rhodniin, a thrombin specific inhibitor from R. prolixus bug. In addition, LDTI can also inhibit both HIV-1 replication in HUT-78 cells trypsin and chymotrypsin, while no other serine proteinases.
LDTI scaffold is a useful source for generating new protease inhibitors and promoting a better understanding of enzyme-inhibitor interactions. Undergoing appropriate display technology and mutation strategy, LDTI scaffold libraries can be generated and selected for potent protease inhibitors. According to relevant reports, there were three different kinds of protease inhibitors developed through LDTI scaffold library, typical examples for these three classes including LDTI-5T, a strong trypsin and thrombin inhibitor; LDTI-29E, a potent and specific neutrophil elastase inhibitor without affecting other tested enzymes and LDTI-2Pl, the strongest plasmin inhibitor in the LDTI mutant library. In this way, LDTI seems feasible to be treated as a unique template scaffold to build combinatorial libraries for generating specific serine proteinase inhibitors suitable for drug design and enzyme-inhibitor interaction studies.
Scientists from Creative Biolabs have applied Hi-Affi™ phage display platform for our scaffold libraries construction. This innovative platform is an improved exogenous gene expression method based on phage display technology, in which a target of interest can be displayed on the surface of bacteriophage coat proteins. In the development of Hi-Affi™ platform, our scientists have combined the trimer codon technology and NNK methods together to increase the diversity and affinity of specific protein scaffolds. As a result, our scaffold libraries can obtain 100% precise mutant and over 1010 diversity.
With long-term extensive experience in the field of scaffold library construction, Creative Biolabs is committed to supplying high affinity and good quality scaffold libraries with our extensive expertise to facilitate customers’ research achievements. Moreover, our scientists are also confident in providing more efficient and faster service with the complete research solution including the library building and its upstream or downstream related products.
Fig. 1 Complex of leech-derived tryptase inhibitor with porcine trypsin. (PDB ID: 1LDT)