The excision of N terminal two amino acids of a novel human parathyroid hormone analog with dipeptidylpeptidase

Abstract

Abstract. hPTH(1-34)-Pro-Pro-Asp (hPTH') is more effective than hPTH(1-34) in the treatment of osteoporosis in our previous studies. The hypothesis that the active form of hPTH' was introduced by the excision with dipeptidyl peptidase IV (DPPIV) in vivo was validated in the present study. Following the determinations of DPPIV activities in rats tissues and serum, the N-terminus dipeptides of hPTH' were excised by DPPIV in rats tissues and serum and the excision production was determined by Tris-Tricine-SDS-PAGE. The results indicated that the N-terminus dipeptides of hPTH' could be excised with DPPIV in rats tissues and serum. The molecular weight of excision production was greater than that of hPTH (1-34) and less than that of hPTH'. In addition, the excision production was injected to mice for detecting its effect on serum calcium of mice. The results suggested that the serum calcium levels of mice treated with hPTH' were similar with those of mice treated with hPTH (1-34). In conclusion, appearing to function as a prodrug, the active form of hPTH' was introduced by the excision with DPPIV in vivo.