A monoclonal antibody to human angiogenin. Inhibition of ribonucleolytic and angiogenic activities and localization of the antigenic epitope.
A monoclonal antibody (mAb) to human angiogenin, a protein that induces formation of new blood vessels, was produced by somatic cell fusion techniques and designated as 26-2F. It is an IgGl kappa whose binding affinity, expressed as an IC50, is (1.6 +/- 0.1) x 10(-9) M as determined by a competition radioimmunoassay. mAb 26-2F neutralizes the ribonucleolytic activity of angiogenin as assessed by in vitro protein synthesis and tRNA degradation assays. It also effectively inhibits neovascularization induced by angiogenin on the chick chorioallantoic membrane. Epitope mapping indicates that the binding region of angiogenin recognized by mAb 26-2F is discontinuous and involves both Trp-89 and residues in the segment 38-41. This epitope is formed by two surface loops which are juxtaposed in the three-dimensional structure of human angiogenin recently determined by X-ray crystallography. Thus mAb 26-2F, along with similar antibodies under investigation, will facilitate structure/function studies of angiogenin, help define its physiological role, and lead to an understanding of the consequences of its inhibition in pathological situations in which angiogenin may be involved.
Fett
J W
JW
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, Massachusetts 02115.
Olson
K A
KA
Rybak
S M
SM
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D002478:Cells, Cultured; D002642:Chick Embryo; D006224:Cricetinae; D003429:Cross Reactions; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000032:analysis* / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D011506:Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D012259:Ribonuclease, Pancreatic; D012260:Ribonucleases / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D000911:Antibodies, Monoclonal; D000939:Epitopes; D011506:Proteins; D012260:Ribonucleases; C046366:angiogenin; D012259:Ribonuclease, Pancreatic