Collagen cross-links. Synthesis of immunoreagents for development of assays for deoxypyridinoline, a marker for diagnosis of osteoporosis

(+)-Deoxypyridinoline (Dpd, 2) is across-link: of bone collagen, which is r eleased and excreted in urine during process of bone resorption. It has bee n shown that this bone collagen degradation product, Dpd (2) is a useful ma rker for diagnosis of osteoporosis and other metabolic bone diseases. In th is paper, the design and synthesis of two immunogens(3, 4) via of conjugati on of succinimidyl ester (14) to carrier protein, bovine serum albumin, or keyhole limphet hemocyanin, was presented. Additionally, fluorescent (5) an d chemiluminescent (6) tracers were prepared from (-);acid (13) via in situ activation and subsequent reaction with 6-Fln-CH2NH2 (17) or Acr-NH2 (18) and hydrolysis. The key hapten (--)-acid (13) was prepared by quaternizatio n of 3-hydroxypyridine derivative (S,S)-(-)-11 with iodide (S)-(-)-10 follo wed by selective hydrolysis. These immunreagents (immunogens 3 and 4 and tr acers 5 and 6) are useful for the development of sensitive and high through put immunoassays, such as FPIA and CLIA for Dpd (2).