No abstract

In the 7 years since the first publications describing phage-displayed peptide libraries, phage display has been successfully employed in a variety of research. Innovations in vector design and methods to identify target clones account for much of this success. At the same time, not all ventures have been entirely successful and it appears that phage and host biology play important roles in this. A key issue concerns the role played by a displayed peptide or protein in its successful expression and incorporation into virions. While few studies have examined these issues specifically in context of phage display, the literature as a whole provides insight. Accordingly, we review phage biology, relevant aspects of host biology, and phage display applications with the goals of illustrating (i) relevant aspects of the interplay between phage-host biology and successful phage display and (ii) the limitations and considerable potential of this important technology.

Analyses of databases derived from the Brookhaven Protein Data Bank have identified a set of related turn structures formed by the sequence Asx-Pro-Xxx(n). In a variety of flanking structural contexts, more than 60% of Asx-Pro sequences adopt a turn conformation stabilized by a set of alternative hydrogen bonds among the side chain O delta and backbone C = O carbonyl oxygens of Asx (residue i) and the backbone NH of residues i + 2, i + 3 and in some cases i + 4. In contrast, the structures adopted by Ser-Pro, His-Pro and other Xxx-Pro sequences reflect more heterogeneous hydrogen-bonding patterns. As expected, structures formed by Asx-Pro-Asx are similar to those formed by Asx-Pro-Xxx(n), but in some cases additional hydrogen bonds are formed between the Asx side chains. Hydrogen bond patterns within Asx-Pro and Asn-Pro-Asn turns are consistent with published NMR studies of helical (Asn-Pro-Asn-Ala)n peptides, indicating that a consensus structure reflecting these hydrogen bonds can serve as a partial model of the Asn-Pro-Asn-Ala tetrapeptide repeats of Plasmodium falciparum circumsporozoite protein.

In the 7 years since the first publications describing phage-displayed peptide libraries, phage display has been successfully employed in a variety of research. Innovations in vector design and methods to identify target clones account for much of this success. At the same time, not all ventures have been entirely successful and it appears that phage and host biology play important roles in this. A key issue concerns the role played by a displayed peptide or protein in its successful expression and incorporation into virions. While few studies have examined these issues specifically in context of phage display, the literature as a whole provides insight. Accordingly, we review phage biology, relevant aspects of host biology, and phage display applications with the goals of illustrating (i) relevant aspects of the interplay between phage-host biology and successful phage display and (ii) the limitations and considerable potential of this important technology.

No abstract