title: Major histocompatibility complex class II binding characteristics of peptoid-peptide hybrids.
abstract: The major histocompatibility complex (MHC) class II binding requirements for solvent-exposed peptide residues were systematically studied using amino acid and peptoid substitutions. In a peptoid residue, the side chain is present on the backbone nitrogen atom as opposed to the alpha-carbon atom in an amino acid residue. To investigate the effect of this side chain shifting on MHC binding, three amino acids in the central part of the peptide sticking out of the binding groove were replaced by corresponding peptoid residues. Two peptoid-peptide hybrids showed large affinity decreases in the MHC-peptide binding assay. To investigate this affinity loss, the individual contributions to MHC binding affinity of the side chain (position), the putative hydrogen bond, and the flexibility were dissected. We conclude that the side chain position as well as the backbone nitrogen atom hydrogen bonding features of solvent-exposed residues in the peptide can be important for MHC binding affinity.
authors.affiliation: Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508, TB Utrecht, The Netherlands.
authors.forename: Ellen C
authors.initials: EC
authors.lastname: de Haan
authors.forename: Marca H M
authors.initials: MH
authors.lastname: Wauben
authors.forename: Mayken C
authors.initials: MC
authors.lastname: Grosfeld-Stulemeyer
authors.forename: John A W
authors.initials: JA
authors.lastname: Kruijtzer
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Liskamp
authors.forename: Ed E
authors.initials: EE
authors.lastname: Moret
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D034444:Peptoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D018583:Pliability; D011485:Protein Binding; D011487:Protein Conformation; D012997:Solvents
chemical_list: D000596:Amino Acids; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D034444:Peptoids; D012997:Solvents