Peptides seldom retain stable conformations if separated from their native protein structure. In an immunological context, this potentially affects the development of selective peptide-based bioprobes and, from a vaccine perspective, poses inherent limits in the elicitation of cross-reactive antibodies by candidate epitopes. Here, a 1,4-disubstituted-1,2,3-triazole-mediated stapling strategy was used to stabilize the native alpha-helical fold of the Pal3 peptidic epitope from the protein antigen Pal(Bp) (BPSL2765) from Burkholderia pseudomallei, the etiological agent of melioidosis. Whereas Pal3 shows no propensity to fold outside its native protein context, the engineered peptide (Pal3H) forms a stable alpha-helix, as assessed by MD, NMR, and CD structural analyses. Importantly, Pal3H shows an enhanced ability to discriminate between melioidosis patient subclasses in immune sera reactivity tests, demonstrating the potential of the stapled peptide for diagnostic purposes. With regard to antibody elicitation and related bactericidal activities, the linear peptide is shown to elicit a higher response. On these bases, we critically discuss the implications of epitope structure engineering for diagnostic- and vaccine-oriented applications.

Flexible vs Rigid Epitope Conformations for Diagnostic- and Vaccine-Oriented Applications : Novel Insights from the Burkholderia pseudomallei BPSL2765 Pal3 Epitope / A. Gori, C. Peri, G. Quilici, A. Nithichanon, D. Gaudesi, R. Longhi, L. Gourlay, M. Bolognesi, G. Lertmemongkolchai, G. Musco, G. Colombo. - In: ACS INFECTIOUS DISEASES. - ISSN 2373-8227. - 2:3(2016), pp. 221-230. [10.1021/acsinfecdis.5b00118]

Flexible vs Rigid Epitope Conformations for Diagnostic- and Vaccine-Oriented Applications : Novel Insights from the Burkholderia pseudomallei BPSL2765 Pal3 Epitope

A. Gori;C. Peri;D. Gaudesi;L. Gourlay;M. Bolognesi;
2016

Abstract

Peptides seldom retain stable conformations if separated from their native protein structure. In an immunological context, this potentially affects the development of selective peptide-based bioprobes and, from a vaccine perspective, poses inherent limits in the elicitation of cross-reactive antibodies by candidate epitopes. Here, a 1,4-disubstituted-1,2,3-triazole-mediated stapling strategy was used to stabilize the native alpha-helical fold of the Pal3 peptidic epitope from the protein antigen Pal(Bp) (BPSL2765) from Burkholderia pseudomallei, the etiological agent of melioidosis. Whereas Pal3 shows no propensity to fold outside its native protein context, the engineered peptide (Pal3H) forms a stable alpha-helix, as assessed by MD, NMR, and CD structural analyses. Importantly, Pal3H shows an enhanced ability to discriminate between melioidosis patient subclasses in immune sera reactivity tests, demonstrating the potential of the stapled peptide for diagnostic purposes. With regard to antibody elicitation and related bactericidal activities, the linear peptide is shown to elicit a higher response. On these bases, we critically discuss the implications of epitope structure engineering for diagnostic- and vaccine-oriented applications.
epitope engineering; peptide stapling; melioidosis; structural vaccinology; bioprobes; antigen design
Settore BIO/10 - Biochimica
ACS INFECTIOUS DISEASES
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/372436
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