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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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mHABP electron density. Side-chain atoms for p2, p3, p5, p7 and p8 in 25608.37 and 10022.43.The figure shows the side-chains for upwardly-oriented residues pointing to TCR-contacting residues. Polar amino acids present in p2, p5 and p8, displaying their non-bonding free electron pairs and π orbital surfaces shown in blurred red while σ orbitals for apolar ones present in p3 and p7 are shown by yellow surfaces. The φ angles (≤ -64°) in p7P (25608.37), p5P (32958.2), p7P (24254.31), p3P and p8P (10022.43) oriented this residue to make contact with the TCR.
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pone.0123249.g009: mHABP electron density. Side-chain atoms for p2, p3, p5, p7 and p8 in 25608.37 and 10022.43.The figure shows the side-chains for upwardly-oriented residues pointing to TCR-contacting residues. Polar amino acids present in p2, p5 and p8, displaying their non-bonding free electron pairs and π orbital surfaces shown in blurred red while σ orbitals for apolar ones present in p3 and p7 are shown by yellow surfaces. The φ angles (≤ -64°) in p7P (25608.37), p5P (32958.2), p7P (24254.31), p3P and p8P (10022.43) oriented this residue to make contact with the TCR.

Mentions: It is worth noting that All IMPIPS had specific electron density regarding upwardly-pointing or TCR-contacting residues, i.e. all had charged residues in p2 with π orbitals (His) or non-bonding free electron pairs (Ser, Asn, Thr, Gln); likewise, all were aliphatic (Leu, Val, Met, Ala) or small apolar (Gly and Pro) residues in p3. All p5 residues were charged with non-bonding free electron pairs or upwardly-pointing Pro, similar to p8 residues having the same characteristics or π electro-resonant structures. No relevant electrostatic preference was identified in p7 but they display a gauche+ orientation (Fig 1). These striking differences suggested that TCR CDR-contacting residues had a specific electron and rotamer orientation preferences (Fig 9 and Fig 1).


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)

mHABP electron density. Side-chain atoms for p2, p3, p5, p7 and p8 in 25608.37 and 10022.43.The figure shows the side-chains for upwardly-oriented residues pointing to TCR-contacting residues. Polar amino acids present in p2, p5 and p8, displaying their non-bonding free electron pairs and π orbital surfaces shown in blurred red while σ orbitals for apolar ones present in p3 and p7 are shown by yellow surfaces. The φ angles (≤ -64°) in p7P (25608.37), p5P (32958.2), p7P (24254.31), p3P and p8P (10022.43) oriented this residue to make contact with the TCR.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123249.g009: mHABP electron density. Side-chain atoms for p2, p3, p5, p7 and p8 in 25608.37 and 10022.43.The figure shows the side-chains for upwardly-oriented residues pointing to TCR-contacting residues. Polar amino acids present in p2, p5 and p8, displaying their non-bonding free electron pairs and π orbital surfaces shown in blurred red while σ orbitals for apolar ones present in p3 and p7 are shown by yellow surfaces. The φ angles (≤ -64°) in p7P (25608.37), p5P (32958.2), p7P (24254.31), p3P and p8P (10022.43) oriented this residue to make contact with the TCR.
Mentions: It is worth noting that All IMPIPS had specific electron density regarding upwardly-pointing or TCR-contacting residues, i.e. all had charged residues in p2 with π orbitals (His) or non-bonding free electron pairs (Ser, Asn, Thr, Gln); likewise, all were aliphatic (Leu, Val, Met, Ala) or small apolar (Gly and Pro) residues in p3. All p5 residues were charged with non-bonding free electron pairs or upwardly-pointing Pro, similar to p8 residues having the same characteristics or π electro-resonant structures. No relevant electrostatic preference was identified in p7 but they display a gauche+ orientation (Fig 1). These striking differences suggested that TCR CDR-contacting residues had a specific electron and rotamer orientation preferences (Fig 9 and Fig 1).

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