[Fragments of human chorionic gonadotropin (hCG): diagnosis of pregnancy and tumors].
The pregnancy and tumor marker human chorionic gonadotropin (hCG) belongs to the family of the glycoprotein hormones. Information on epitope forming sequences of hCG and its subunits hCG alpha and hcg beta has significant impact on the examination of intra- and extracellular metabolism and the standardization of diagnostic assay systems. Variants of hCG appear in biological fluids with variable modifications on different parts of the molecule. These changes may influence the binding patterns of monoclonal antibodies (MCA), thereby causing erroneous results in hCG immunoassays. The aim of the present work was to investigate the influence of peptide bond cleavages and the loss of certain segments of the molecule, which were induced by proteases on the expression of the seven hCG alpha-(alpha 1-alpha 7), nine hCG beta- (beta 1-beta 9) and four hCG beta-core-fragment-epitopes (beta 10-beta 13), previously identified by us [1-10]. To this end, we digested hCG alpha and hCG beta with chymotrypsin. Hormone fragments were separated by high performance liquid chromatography (HPLC) and subsequently immunochemically examined by direct binding radioimmunoassay (DB-RIA), competitive RIA and immunoenzymometric assays (IEMA). Fractions containing hCG-like immunoreactivity were sequenced by Edman and carboxypeptidase-Y degradation. It appeared that: (I) Amino acids (AA) alpha 41-47 and the peptide bonds between AA alpha 40/41, alpha 47/48 and alpha 29/30 do not influence the expression of the 7 alpha-epitopes, (II) The absence of the hCG beta N-terminus plays a crucial role for the formation of epitopes beta 10 and beta 13. (III) Neither the presence nor the absence of the C-terminal peptide of hCG beta (hCG beta CTP, AA beta 114-145) has any importance for the expression of epitopes beta 1-beta 7 and beta 10-beta 13 (IV).(ABSTRACT TRUNCATED AT 250 WORDS)
Lechner
O
O
Institut für Biomedizinische Alternsforschung, Osterreichische Akademie der Wissenschaften, Innsbruck.
Dirnhofer
S
S
Gerth
R
R
Merz
W E
WE
Wick
G
G
Berger
P
P
D014408:Biomarkers, Tumor / Q000652:urine*; D002822:Choriocarcinoma / Q000175:diagnosis* / Q000652:urine; D006063:Chorionic Gonadotropin / Q000652:urine*; D002918:Chymotrypsin; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010446:Peptide Fragments / Q000652:urine*; D011247:Pregnancy; D011259:Pregnancy Tests, Immunologic; D013329:Structure-Activity Relationship; D013736:Testicular Neoplasms / Q000175:diagnosis* / Q000652:urine; D014594:Uterine Neoplasms / Q000175:diagnosis* / Q000652:urine
D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D010446:Peptide Fragments; D002918:Chymotrypsin
Fragmente des humanen Choriongonadotropins (hCG): Schwangerschafts- und Tumordiagnostik.