title: Immunological effects of an arginine side chain contaminating synthetically prepared peptides.
abstract: The side chain, 4-methoxy-2,3,6-trimethylbenzenesulphonyl (Mtr), is a protective group coupled to arginine to mask the omega-nitrogen, in order to protect the guanidino function during peptide synthesis by the 9-fluorenylmethoxycarbonyl (Fmoc) procedure (Walker, 1994). This group is removed at the completion of peptide synthesis; however, the cleavage process can be incomplete. We have found that animals injected with a mixed population of pure, i.e. unmodified, and Mtr-containing MBP peptides have an immunodominant humoral response to the Mtr-bearing peptide. This response is dependent on the characteristics of the MBP peptide involved. For two MBP peptides, the Mtr-containing peptide had increased binding to antibody over pure peptide. For two other peptides, only the Mtr-containing peptide bound antibody while the unmodified peptide did not. In a separate system involving a polyclonal response to an unrelated peptide from beta2-microglobulin (beta2 m), the dominance of the Mtr group was also evident. These results provide further evidence that a small side chain on a single amino acid in a peptide can markedly alter the immunogenicity and antigenicity of that peptide for antibody reactivity. This evidence emphasizes the need for a critical awareness of each component of peptide synthesis and its potential to alter the immunoreactivity of the final product.
authors.affiliation: The Department of Neurology, University of Alabama at Birmingham, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Schlagel
authors.forename: L
authors.initials: L
authors.lastname: Bors
authors.forename: G W
authors.initials: GW
authors.lastname: Mitchell
authors.forename: J L
authors.initials: JL
authors.lastname: King
authors.forename: L
authors.initials: L
authors.lastname: Cao
authors.forename: M
authors.initials: M
authors.lastname: Kirk
authors.forename: J N
authors.initials: JN
authors.lastname: Whitaker
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001120:Arginine / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D005449:Fluorenes / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000138:chemical synthesis / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000276:immunology*
chemical_list: D000596:Amino Acids; D000911:Antibodies, Monoclonal; D000939:Epitopes; D005449:Fluorenes; D004676:Myelin Basic Protein; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D013450:Sulfones; D001120:Arginine