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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.

Show MeSH
Ring structure formation in mHABP 25608.37.H-bonds or vdW interactions between Ser2 25608.37 N and O backbone atoms and HLA-DRβ1*0404/0401 conserved Nβ82 side-chain atoms; this led to establishing ring structures involving the 11 atoms shown here. These 9–11 ring atoms structures were also established with Qα9, Nα62 and Nα69, thereby stabilising IMPIPS binding to the HLA-DRβ1* PBR.
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pone.0123249.g008: Ring structure formation in mHABP 25608.37.H-bonds or vdW interactions between Ser2 25608.37 N and O backbone atoms and HLA-DRβ1*0404/0401 conserved Nβ82 side-chain atoms; this led to establishing ring structures involving the 11 atoms shown here. These 9–11 ring atoms structures were also established with Qα9, Nα62 and Nα69, thereby stabilising IMPIPS binding to the HLA-DRβ1* PBR.

Mentions: This confirmed previous results which had shown that HLA-DRβ1* and Aona DRβ1* conserved Nβ82, Qα9, Nα69 and Nα62 formed 9–11 atom ring structures (Fig 8) with VHLLAI and HIPI backbone atoms to establish the necessary 9–11 canonical H-bonds or vdW interactions (Fig 7) for properly anchoring mHABPs to the MHCII PBR. The foregoing, together with the bonds established by Sα53 with—p1, the variable (T, R, N or K) β71 residues and conserved Wβ61 (thereby establishing one H-bond each with the peptide’s backbone) might lead to very strong, stable pMHCII complex formation to be presented to the TCR for inducing an appropriate immune response, as previously shown for antigenic peptides (Figs 7 and 8 and Supporting Information (S1 Fig)).


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)

Ring structure formation in mHABP 25608.37.H-bonds or vdW interactions between Ser2 25608.37 N and O backbone atoms and HLA-DRβ1*0404/0401 conserved Nβ82 side-chain atoms; this led to establishing ring structures involving the 11 atoms shown here. These 9–11 ring atoms structures were also established with Qα9, Nα62 and Nα69, thereby stabilising IMPIPS binding to the HLA-DRβ1* PBR.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123249.g008: Ring structure formation in mHABP 25608.37.H-bonds or vdW interactions between Ser2 25608.37 N and O backbone atoms and HLA-DRβ1*0404/0401 conserved Nβ82 side-chain atoms; this led to establishing ring structures involving the 11 atoms shown here. These 9–11 ring atoms structures were also established with Qα9, Nα62 and Nα69, thereby stabilising IMPIPS binding to the HLA-DRβ1* PBR.
Mentions: This confirmed previous results which had shown that HLA-DRβ1* and Aona DRβ1* conserved Nβ82, Qα9, Nα69 and Nα62 formed 9–11 atom ring structures (Fig 8) with VHLLAI and HIPI backbone atoms to establish the necessary 9–11 canonical H-bonds or vdW interactions (Fig 7) for properly anchoring mHABPs to the MHCII PBR. The foregoing, together with the bonds established by Sα53 with—p1, the variable (T, R, N or K) β71 residues and conserved Wβ61 (thereby establishing one H-bond each with the peptide’s backbone) might lead to very strong, stable pMHCII complex formation to be presented to the TCR for inducing an appropriate immune response, as previously shown for antigenic peptides (Figs 7 and 8 and Supporting Information (S1 Fig)).

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