Peptoid-Peptide Hybrids: Design, Synthesis and MHC Binding

Haan, Ellen C de; Wauben, Marca H. M.; Grosfeld-Stulemeyer, M. C.; Kruijtzer, John A. W.; Liskamp, Rob M. J.; Moret, Ed E.

doi:10.1007/978-94-010-0464-0_489

Cited by 8 publications

(11 citation statements)

References 7 publications

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“…Taken together, our results demonstrate that the bound peptide and surrounding heavy chain residues in class I molecules exhibit a wide range of flexibilities, which are linked to MHC polymorphism. Enhanced peptide flexibilities, however, do not necessarily influence peptide binding affinities (33). Recent findings suggest that peptide residues are mainly involved in pMHC-TCR complex stabilization, allowing efficient T-cell activation (34).…”

Section: Differential Peptide Dynamics Is Linked To Mhc Polymorphismmentioning

confidence: 99%

Differential Peptide Dynamics Is Linked to Major Histocompatibility Complex Polymorphism

Pöhlmann

Böckmann

Grubmüller

et al. 2004

Journal of Biological Chemistry

112

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Section: Differential Peptide Dynamics Is Linked To Mhc Polymorphismmentioning

confidence: 99%

Differential Peptide Dynamics Is Linked to Major Histocompatibility Complex Polymorphism

Pöhlmann

Böckmann

Grubmüller

et al. 2004

Journal of Biological Chemistry

112

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“…Numerous short oligomers (<8-mers) have been found that bind to therapeutically relevant proteins, acting as antagonists, inhibitors, or activators 15–22. Peptoid substitutions into peptides (to make peptide/peptoid hybrids) have been shown to significantly enhance binding affinity 20–22.…”

Section: Introductionmentioning

confidence: 99%

Biomimetic Nanostructures: Creating a High-Affinity Zinc-Binding Site in a Folded Nonbiological Polymer

et al. 2008

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One of the long-term goals in developing advanced biomaterials is to generate protein-like nanostructures and functions from a completely nonnatural polymer. Toward that end, we introduced a high-affinity zinc-binding function into a peptoid (N-substituted glycine polymer) two-helix bundle. Borrowing from well-understood zinc-binding motifs in proteins, thiol and imidazole moieties were positioned within the peptoid such that both helices must align in close proximity to form a binding site. We used fluorescence resonance energy transfer (FRET) reporter groups to measure the change of the distance between the two helical segments and to probe the binding of zinc. We systematically varied the position and number of zinc-binding residues, as well as the sequence and size of the loop that connects the two helical segments. We found that certain peptoid two-helix bundles bind zinc with nanomolar affinities and high selectivity compared to other divalent metal ions. Our work is a significant step toward generating biomimetic nanostructures with enzyme-like functions.

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“…Single amino acid substitutions at a T-cell contact residue can abrogate T-cell recognition (20) or convert agonist peptides into antagonists (21). Modifications of the peptide backbone of class II MHC-binding antigens also have been reported in an effort to increase bioavailability or serum half-life and include alkylation, peptide-bond reduction, and incorporation of peptoid, azapeptide, dipeptide mimetic substitutions, and D-amino acids (8,(22)(23)(24)(25)(26). In general, peptides carrying one or more of these modifications are less effective T-cell activators as compared with a peptide that does not include the modification (23,26,27).…”

mentioning

confidence: 99%

Exploration of the P6/P7 Region of the Peptide-binding Site of the Human Class II Major Histocompatability Complex Protein HLA-DR1

Zavala-Ruiz

Sundberg

Stone

et al. 2003

Journal of Biological Chemistry

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Crystal structures of the class II major histocompatibilty complex (MHC) protein, HLA-DR1, generally show a tight fit between MHC and bound peptide except in the P6/P7 region of the peptide-binding site. In this region, there is a shallow water-filled pocket underneath the peptide and between the pockets that accommodate the P6 and P7 side chains. We investigated the properties of this pocket with the idea of engineering substitutions into the corresponding region of peptide antigens to increase their binding affinity for HLA-DR1. We investigated D-amino acids and N-alkyl modifications at both the P6 and P7 positions of the peptide and found that binding of peptides to HLA-DR1 could be increased by incorporating an N-methyl substitution at position 7 of the peptide. The crystal structure of HLA-DR1 bound to a peptide containing a P7 N-methyl alanine was determined. The N-methyl group orients in the P6/P7 pocket, displacing one of the waters usually bound in this pocket. The structure shows that the substitution does not alter the conformation of the bound peptide, which adopts the usual polyproline type II helix. An antigenic peptide carrying the N-methyl modification is taken up by antigen-presenting cells and loaded onto endogenous class II MHC molecules for presentation, and the resultant MHC-peptide complexes activate antigen-specific Tcells. These results suggest a possible strategy for increasing the affinity of weakly immunogenic peptides that might be applicable to the development of vaccines and diagnostic reagents.

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Peptoid-Peptide Hybrids: Design, Synthesis and MHC Binding

Cited by 8 publications

References 7 publications

Differential Peptide Dynamics Is Linked to Major Histocompatibility Complex Polymorphism

Differential Peptide Dynamics Is Linked to Major Histocompatibility Complex Polymorphism

Biomimetic Nanostructures: Creating a High-Affinity Zinc-Binding Site in a Folded Nonbiological Polymer

Exploration of the P6/P7 Region of the Peptide-binding Site of the Human Class II Major Histocompatability Complex Protein HLA-DR1

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