title: Epitope analysis of human insulin and intact proinsulin.
abstract: Residues belonging to epitopes on human insulin that were recognized by a panel of three monoclonal antibodies were located using mutated insulins and insulins from a number of different animal species. Epitopes on human proinsulin recognized by two monoclonal antibodies were also identified using partially processed proinsulin species. Epitopes were located on the C-A and B-C junctions of proinsulin and on the N-termini of the A- and B-chains and the central region of the B-chain of human insulin. Antibodies that bound proinsulin were found to induce conformational changes in the prohormone. The presence of a well-defined interaction between the C-peptide portion and the N-terminus of the A-chain of the insulin moiety of intact proinsulin has also been demonstrated. The relevance of these studies to the development of two-site assays for the measurement of partially processed proinsulin species in human sera is also discussed.
authors.affiliation: Department of Chemistry, University of York, Heslington, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Crowther
authors.forename: B
authors.initials: B
authors.lastname: Xiao
authors.forename: P N
authors.initials: PN
authors.lastname: Jørgensen
authors.forename: G G
authors.initials: GG
authors.lastname: Dodson
authors.forename: C N
authors.initials: CN
authors.lastname: Hales
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002417:Cattle; D000939:Epitopes / Q000737:chemistry*; D006736:Horses; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008958:Models, Molecular; D011384:Proinsulin / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011487:Protein Conformation; D012756:Sheep
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D007328:Insulin; D011384:Proinsulin