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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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H-bonds established between HLA-DRβ1*0404/0401 with 25608.37 and HLA-DRβ1*0301 with 10022. A.D. Front view B.E. Top view C. F. Side view.Left panel: 25608.37—HLA-DRβ1*0404/0401. Right-hand Panel: 10022.43—HLA-DRβ1*0301. Their atomic distances are given in S1 Fig.
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pone.0123249.g007: H-bonds established between HLA-DRβ1*0404/0401 with 25608.37 and HLA-DRβ1*0301 with 10022. A.D. Front view B.E. Top view C. F. Side view.Left panel: 25608.37—HLA-DRβ1*0404/0401. Right-hand Panel: 10022.43—HLA-DRβ1*0301. Their atomic distances are given in S1 Fig.

Mentions: NB: 3D structures were determined by two very different methods: 1H-NMR (in solution) for 25608.37 and 10022.43 as the prototype mHABPs and X-ray crystallography for HLA-DRβ1*0401 (PDB code 1J8H) [72] and HLA-DRβ1*0302 (PDB code 1A6A) [25] as templates for docking studies (Fig 7). Some differences could thus have occurred due to the different methodologies used, i.e. HLA-DRβ1*0404/0401-like (Aona DRβ*W4704 GA family) and HLA-DRβ1*0302 (Aona HLA-DRβ1*0305 GA allelic family). HLA-DRβ1*-like structures were modified by molecular dynamics based on the few differences with Aotus [36,40] (golden in HLA-DRβ1* β-chain blue ribbon in Fig 7), no further changes or refinement being needed.


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)

H-bonds established between HLA-DRβ1*0404/0401 with 25608.37 and HLA-DRβ1*0301 with 10022. A.D. Front view B.E. Top view C. F. Side view.Left panel: 25608.37—HLA-DRβ1*0404/0401. Right-hand Panel: 10022.43—HLA-DRβ1*0301. Their atomic distances are given in S1 Fig.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123249.g007: H-bonds established between HLA-DRβ1*0404/0401 with 25608.37 and HLA-DRβ1*0301 with 10022. A.D. Front view B.E. Top view C. F. Side view.Left panel: 25608.37—HLA-DRβ1*0404/0401. Right-hand Panel: 10022.43—HLA-DRβ1*0301. Their atomic distances are given in S1 Fig.
Mentions: NB: 3D structures were determined by two very different methods: 1H-NMR (in solution) for 25608.37 and 10022.43 as the prototype mHABPs and X-ray crystallography for HLA-DRβ1*0401 (PDB code 1J8H) [72] and HLA-DRβ1*0302 (PDB code 1A6A) [25] as templates for docking studies (Fig 7). Some differences could thus have occurred due to the different methodologies used, i.e. HLA-DRβ1*0404/0401-like (Aona DRβ*W4704 GA family) and HLA-DRβ1*0302 (Aona HLA-DRβ1*0305 GA allelic family). HLA-DRβ1*-like structures were modified by molecular dynamics based on the few differences with Aotus [36,40] (golden in HLA-DRβ1* β-chain blue ribbon in Fig 7), no further changes or refinement being needed.

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