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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

Representative torsion angles (Φ, Ψ, χ1, χ2, χ3 and χ4) in mHABPs involved in mixtures immunised in Aotus monkeys.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.
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pone.0123249.g001: Representative torsion angles (Φ, Ψ, χ1, χ2, χ3 and χ4) in mHABPs involved in mixtures immunised in Aotus monkeys.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.

Mentions: An appropriate mixture of Spz-derived VHLLAI mHABPs having gauche+ orientation in p3 and controlled by HLA-DRβ1* 0404/0401 or DRβ1*11 and 0403-like alleles covering 40% of the wild Aotus population (Fig 1) has thus enabled overcoming the competition, interference or suppression associated with vaccine mixture composition development.


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)

Representative torsion angles (Φ, Ψ, χ1, χ2, χ3 and χ4) in mHABPs involved in mixtures immunised in Aotus monkeys.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.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123249.g001: Representative torsion angles (Φ, Ψ, χ1, χ2, χ3 and χ4) in mHABPs involved in mixtures immunised in Aotus monkeys.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.
Mentions: An appropriate mixture of Spz-derived VHLLAI mHABPs having gauche+ orientation in p3 and controlled by HLA-DRβ1* 0404/0401 or DRβ1*11 and 0403-like alleles covering 40% of the wild Aotus population (Fig 1) has thus enabled overcoming the competition, interference or suppression associated with vaccine mixture composition development.

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