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IMPIPS: the immune protection-inducing protein structure concept in the search for steric-electron and topochemical principles for complete fully-protective chemically synthesised vaccine development.

Patarroyo ME, Bermúdez A, Alba MP, Vanegas M, Moreno-Vranich A, Poloche LA, Patarroyo MA - PLoS ONE (2015)

Bottom Line: Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1* structures.They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ1*-peptide binding regions (PBR).Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response.

View Article: PubMed Central - PubMed

Affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Universidad Nacional de Colombia, Bogotá, Colombia.

ABSTRACT
Determining immune protection-inducing protein structures (IMPIPS) involves defining the stereo-electron and topochemical characteristics which are essential in MHC-p-TCR complex formation. Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1* structures. They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ1*-peptide binding regions (PBR). Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response. Immunological assays in Aotus monkeys involving IMPIPS mixtures led to promising results; taken together with the aforementioned physicochemical principles, non-interfering, long-lasting, protection-inducing, multi-epitope, multistage, minimal subunit-based chemically-synthesised peptides can be designed against diseases scourging humankind.

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Related in: MedlinePlus

Spz- and Mrz-derived mHABP fragments binding to the HLA-DRβ1* PBR.Side view of mHABPs binding to the HLA-DRβ1* PBR (as assessed by 1H-NMR) displaying the residues according to the colour code: p1 (fuchsia), p2 (red), p3 (pale blue), p4 (dark blue), p5 (pink), p6 (orange), p7 (grey), p8 (yellow) and p9 (green). The dotted balls in light green represent the nonbonding free electron pairs able to establish H bonds with the HLA-DRβ1*PBR residues. The pink planes mark peptide bonds.
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pone.0123249.g003: Spz- and Mrz-derived mHABP fragments binding to the HLA-DRβ1* PBR.Side view of mHABPs binding to the HLA-DRβ1* PBR (as assessed by 1H-NMR) displaying the residues according to the colour code: p1 (fuchsia), p2 (red), p3 (pale blue), p4 (dark blue), p5 (pink), p6 (orange), p7 (grey), p8 (yellow) and p9 (green). The dotted balls in light green represent the nonbonding free electron pairs able to establish H bonds with the HLA-DRβ1*PBR residues. The pink planes mark peptide bonds.

Mentions: Grey shows the PPIIL region, yellow shows the β-turn region and green an α-helix conformation. Purple box, χ1 angles for p3 and p7, and χ2 angles for p5, highlighting their gauche+ rotamer orientation. The colours of residues vertically displayed in each mHABP correspond to the code for Fig 3.


IMPIPS: the immune protection-inducing protein structure concept in the search for steric-electron and topochemical principles for complete fully-protective chemically synthesised vaccine development.

Patarroyo ME, Bermúdez A, Alba MP, Vanegas M, Moreno-Vranich A, Poloche LA, Patarroyo MA - PLoS ONE (2015)

Spz- and Mrz-derived mHABP fragments binding to the HLA-DRβ1* PBR.Side view of mHABPs binding to the HLA-DRβ1* PBR (as assessed by 1H-NMR) displaying the residues according to the colour code: p1 (fuchsia), p2 (red), p3 (pale blue), p4 (dark blue), p5 (pink), p6 (orange), p7 (grey), p8 (yellow) and p9 (green). The dotted balls in light green represent the nonbonding free electron pairs able to establish H bonds with the HLA-DRβ1*PBR residues. The pink planes mark peptide bonds.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400017&req=5

pone.0123249.g003: Spz- and Mrz-derived mHABP fragments binding to the HLA-DRβ1* PBR.Side view of mHABPs binding to the HLA-DRβ1* PBR (as assessed by 1H-NMR) displaying the residues according to the colour code: p1 (fuchsia), p2 (red), p3 (pale blue), p4 (dark blue), p5 (pink), p6 (orange), p7 (grey), p8 (yellow) and p9 (green). The dotted balls in light green represent the nonbonding free electron pairs able to establish H bonds with the HLA-DRβ1*PBR residues. The pink planes mark peptide bonds.
Mentions: Grey shows the PPIIL region, yellow shows the β-turn region and green an α-helix conformation. Purple box, χ1 angles for p3 and p7, and χ2 angles for p5, highlighting their gauche+ rotamer orientation. The colours of residues vertically displayed in each mHABP correspond to the code for Fig 3.

Bottom Line: Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1* structures.They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ1*-peptide binding regions (PBR).Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response.

View Article: PubMed Central - PubMed

Affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Universidad Nacional de Colombia, Bogotá, Colombia.

ABSTRACT
Determining immune protection-inducing protein structures (IMPIPS) involves defining the stereo-electron and topochemical characteristics which are essential in MHC-p-TCR complex formation. Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1* structures. They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ1*-peptide binding regions (PBR). Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response. Immunological assays in Aotus monkeys involving IMPIPS mixtures led to promising results; taken together with the aforementioned physicochemical principles, non-interfering, long-lasting, protection-inducing, multi-epitope, multistage, minimal subunit-based chemically-synthesised peptides can be designed against diseases scourging humankind.

Show MeSH
Related in: MedlinePlus