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Peptides have the potential for targeting vaccines against pre-specified epitopes on folded proteins. When polyclonal antibodies against native proteins are used to screen peptide libraries, most of the peptides isolated align to linear epitopes on the proteins. The mechanism of cross-reactivity is unclear; both structural mimicry by the peptide and induced fit of the epitope may occur. The most effective peptide mimics of protein epitopes are likely to be those that best mimic both the chemistry and the structure of epitopes. Our goal in this work has been to establish a strategy for characterizing epitopes on a folded protein that are candidates for structural mimicry by peptides. We investigated the chemical and structural bases of peptide-protein cross-reactivity using phage-displayed peptide libraries in combination with computational structural analysis. Polyclonal antibodies against the well-characterized antigens, hen eggwhite lysozyme and worm myohemerythrin, were used to screen a panel of phage-displayed peptide libraries. Most of the selected peptide sequences aligned to linear epitopes on the corresponding protein; the critical binding sequence of each epitope was revealed from these alignments. The structures of the critical sequences as they occur in other non-homologous proteins were analyzed using the Sequery and Superpositional Structural Assignment computer programs. These allowed us to evaluate the extent of conformational preference inherent in each sequence independent of its protein context, and thus to predict the peptides most likely to have structural preferences that match their protein epitopes. Evidence for sequences having a clear structural bias emerged for several epitopes, and synthetic peptides representing three of these epitopes bound antibody with sub-micromolar affinities. The strong preference for a type II beta-turn predicted for one peptide was confirmed by NMR and circular dichroism analyses. Our strategy for identifying conformationally biased epitope sequences provides a new approach to the design of epitope-targeted, peptide-based vaccines.
L Craig, and
P C Sanschagrin, and
A Rozek, and
S Lackie, and
L A Kuhn, and
J K Scott
December 2002,
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology,
L Craig, and
P C Sanschagrin, and
A Rozek, and
S Lackie, and
L A Kuhn, and
J K Scott
September 1968,
The Journal of physiology,
L Craig, and
P C Sanschagrin, and
A Rozek, and
S Lackie, and
L A Kuhn, and
J K Scott
July 2019,
Journal of agricultural and food chemistry,
L Craig, and
P C Sanschagrin, and
A Rozek, and
S Lackie, and
L A Kuhn, and
J K Scott
July 1995,
Journal of immunology (Baltimore, Md. : 1950),
L Craig, and
P C Sanschagrin, and
A Rozek, and
S Lackie, and
L A Kuhn, and
J K Scott
May 2019,
Journal of biomolecular structure & dynamics,
L Craig, and
P C Sanschagrin, and
A Rozek, and
S Lackie, and
L A Kuhn, and
J K Scott
January 2017,
Protein and peptide letters,
L Craig, and
P C Sanschagrin, and
A Rozek, and
S Lackie, and
L A Kuhn, and
J K Scott
January 2016,
Critical reviews in immunology,
L Craig, and
P C Sanschagrin, and
A Rozek, and
S Lackie, and
L A Kuhn, and
J K Scott
January 2002,
Allergy,
L Craig, and
P C Sanschagrin, and
A Rozek, and
S Lackie, and
L A Kuhn, and
J K Scott
May 2000,
Electrophoresis,
L Craig, and
P C Sanschagrin, and
A Rozek, and
S Lackie, and
L A Kuhn, and
J K Scott
August 1999,
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology,
