Library Types

Human Antibody Libraries  |   Protein Libraries  |   Structured Peptide Libraries  |   Linear Peptide Libraries  |   Substrate Phage Peptide Library

Human Antibody Libraries
Dyax's human antibody phage libraries combine gene fragments from human donors with strategically designed synthetic DNA. Human-donor-sourced fragments encoding the light-chain variable region and a portion of the heavy-chain variable region are combined with synthetic DNA encoding human antibody sequences with diversity introduced at strategic sites. These diverse gene products are displayed on phage and phagemid libraries as Fab antibody fragments. The library design facilitates the rapid production and purification of soluble Fabs and IgGs, and, if needed, permits affinity maturation. The current generation phagemid-based Fab library displays 35 billion distinct human antibodies and the phage-based Fab library displays 10 billion. These have been used to identify high-affinity human antibodies that bind to numerous therapeutic targets, including cell surface proteins such as tumor cell markers, viral antigens, enzymes, and glycoproteins.

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Protein Libraries
Dyax designs and builds phage libraries based on well-characterized protein structures. A highly structured protein is selected and the amino acids in one portion of this "parental" protein are varied. Only those regions of the protein accessible to the surface are varied because it is these regions that are available for binding of target; regions of the protein involved in maintaining its structure are not varied. Using this approach, Dyax has created libraries including Kunitz domains.

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Structured Peptide Libraries
Dyax has created a number of small, disulfide-constrained cyclic peptide libraries. The peptides within the cyclic structure range in size from six to twelve amino acids. Amino acids both within and outside the cyclic structure are selected for variation, and the number of distinct peptide structures in each library typically exceeds 1 billion. In total, these libraries contain about 10 billion distinct peptides. Validated against many different targets, these libraries are preferred for in vivo imaging and affinity separations applications. The resulting peptides are chemically synthesizable and amendable to chemical modification, such as attachment to a chromatographic support.

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Linear Peptide Libraries
Dyax has designed and built a linear peptide library where all 19 amino acids (no cysteine) at each position in a 20-mer peptide are allowed to create a library of 10 billion peptides. Dyax has also designed peptide substrate libraries, which contain variations in the peptide sequence that serves as the recognition site for serine proteases. Dyax has used its peptide libraries to identify novel linear peptides that may be used as therapeutics or as affinity ligands for the purification of therapeutic targets. Dyax has used its peptide substrate libraries to identify novel peptides that are better substrates for proteases; some of these peptides are being used for large-scale protein purification.

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Substrate Phage Peptide Library
Dyax has designed and built a substrate phage peptide library where all 19 amino acids (no cysteine) at each position in a 13-mer peptide are allowed to create a library of approximately 100 million peptides. This 13-mer region contains variations in the peptide sequence that serves as the recognition site for proteases.  Dyax has used its peptide substrate libraries to identify novel peptides that are better substrates for proteases as compared to their native substrates. In some cases, Dyax has identified substrates to novel orphan proteases, where their native substrate is not known.

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