A novel human parathyroid hormone (1-34) analog for the treatment of osteoporosis.
The more effective bioactive peptides which can be efficiently prepared with low cost and high yield are in great demand for the development of therapeutic peptides. In this study, Pro-Pro-[Arg(11)]hPTH(1-34)-Pro-Pro-Asp (hPTH'), an analog of human parathyroid hormone (1-34) [hPTH(1-34)], was prepared by an efficiently cost-effective preparation strategy. It was repeated eight times on the gene level and expressed in the form of inclusion bodies in Escherichia coli. Following some primary purifications, the inclusion bodies of octapeptide repeats were hydrolyzed into hPTH' monomers by hydrochloric acid. After further purified by a CM52 chromatographic column, hPTH' reached a yield of 16.9% and output of 61 mg/l medium. Furthermore, we compared anabolic effects between hPTH' and hPTH(1-34) on ovariectomized rats. The results indicated that hPTH' led to more significant increments in bone material density (BMD), trabecular width and bone formation marker as well as less loss in marrow space area than what hPTH(1-34) did. In addition, the active form of hPTH' was introduced by the excision with dipeptidyl peptidase IV in vivo. These results suggest that hPTH' is more effective than hPTH(1-34) in stimulating bone formation and improving skeletal microarchitecture. We can conclude that hPTH' is potentially a more effective therapeutical agent on osteoporosis.
Feng
Jiao
J
Laboratory of Minigene Pharmacy, School of Life Science and Technology, China Pharmaceutical University, Nanjing, PR China.
Liu
Yanhua
Y
Xing
Yun
Y
Wang
Huaqian
H
Li
Taiming
T
Liu
Jingjing
J
Fan
Hao
H
Cao
Rongyue
R
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D005260:Female; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology; D010281:Parathyroid Hormone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000627:therapeutic use
D010281:Parathyroid Hormone; D011993:Recombinant Fusion Proteins