Combinatorial phage display

Naik, R.R., Brott, L.L., Clarson, S.J. and, Stone, M.O. (2002) Silica-precipitating peptides isolated from a combinatorial phage display peptide library. Journal of Nanoscience and Nanotechnology, 2, 95-100. 

Mayrose I, Shlomi T, Rubinstein ND et al (2007) Epitope mapping using combinatorial phage-display libraries a graph-based algorithm. Nucleic Acids Res 35 69-78... 

It has been shown recently that engineered viruses can recognize specific semiconductor surfaces using the method of selection by combinatorial phage display Whaley R, English DS, Hu EL, Barbara PF, Belcher AM (2000) Nature 405 665... 

We selected scFvs from a combinatorial phage display library using both phosphorylated and nonphosphorylated forms of a C-terminal y-H2AX peptide. Figure 2B shows die peptide sequence used for selection. Ten separate bacteriophage isolates were chosen for further characterization. Soluble scFvs were produced in the periplasm of an E. coli host. Periplasmic extracts were either used direcdy or as a source of material for further purification. 

Alternatively, combinatorial phage display strategies have been used as an efficient mean of selecting inorganic binding peptides that promote the rapid, room temperature precipitation of tailored metal oxide particles. Silver binding peptides were thus identified and found to promote synthesis of silver particles... 

EMPl, selected by phage display from random peptide libraries, demonstrates that a dimer of a 20-residue peptide can mimic the function of a monomeric 166-residue protein. In contrast to the minimized Z domain, this selected peptide shares neither the sequence nor the structure of the natural hormone. Thus, there can be a number of ways to solve a molecular recognition problem, and combinatorial methods such as phage display allow us to sort through a multitude of structural scaffolds to discover novel solutions. 

Protein engineering is now routinely used to modify protein molecules either via site-directed mutagenesis or by combinatorial methods. Factors that are Important for the stability of proteins have been studied, such as stabilization of a helices and reducing the number of conformations in the unfolded state. Combinatorial methods produce a large number of random mutants from which those with the desired properties are selected in vitro using phage display. Specific enzyme inhibitors, increased enzymatic activity and agonists of receptor molecules are examples of successful use of this method. 

Rader, C., and Barbas, C. F., Ill (1997). Phage display of combinatorial antibody libraries. Curr. Opin. Biotechnol. 8, 503-508. 

Sompuram SR, Kodela V, Ramanathan H, et al. Synthetic peptides identified from phage-displayed combinatorial libraries as immunodiagnostic assay surrogate quality-control targets. Clin. Chem. 2002 48 410-420. 

Figure 16.4 Graph depicting the percentage of lysine residues among peptides that bind to the indicated monoclonal antibodies. The peptides were isolated after affinity selection (biopanning) from a phage-displayed combinatorial peptide library. The peptides are grouped as to whether they are susceptible to formalin fixation, resulting in a loss of immunoreactivity.

While in normal combinatorial peptide libraries (either chemical or phage display) each component has a unique sequence that is different from all others, in the cycloscan libraries all components have the same sequence, but differ in their conformation. This conformational diversity is generated in a dendrimeric hierarchy as shown exemplarily in Scheme 27 for the parent linear heptapeptide A-B-C-D-E-F-G. The diversity of the 1st order sublibrary (this nomenclature was adopted from Furka[468l) is based on the mode of cyclization. Excluding the head-to-tail cyclization there are seven different modes of cyclization that can be used for cycloscan three natural modes of cyclization and four modes of N-backbone cyclization. In addition there are five theoretical modes of C-backbone cyclization (see Scheme 1) which are not included in Scheme 27. 

Figure 8. Selection of the phage from the phage-displayed combinatorial peptide library [9]...

Catalytic antibodies, like enzymes, must be isolated and purified to homogeneity before they can be studied. Initially this was done by using the hybridoma technique for isolation of monoclonal antibodies (Box 31-A). After induction of antibody formation by injecting a selected hapten into a mouse, large numbers of monoclonal antibodies had to be tested for catalytic activity. Even if several thousand different monoclonal antibodies were tested, only a few with catalytic properties could be found.1 Newer methods have incorporated recombinant DNA techniques (Box 31-A) and use of combinatorial libraries and phage display.) Incorporation of acidic or basic groups into the haptens used to induce antibody formation may yield antibodies capable of mimicking the acid-base catalysis employed by natural enzymes. 0... 

Tsurushita, N., Fu, H., and Warren, C. (1996) Phage display vectors for in vivo recombination of immunoglobulin heavy and light chain genes to make large combinatorial libraries. Gene 172, 59-63. 

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