STRUCTURE-FUNCTION RELATIONSHIP OF ANALOGUES OF PTH(1-11) CONTAINING A COMBINATION OF AIB AND (αMe)VAL

摘要

Parathyroid hormone (PTH) is an 84 amino acid peptide hormone. Produced in the parathyroid glands, it acts primarily on bone and kidney to maintain extracellular calcium levels within normal limits. It has been shown that the first 34-amino acid fragment of PTH is sufficient to bind and activate the PTH type I receptor (PTH1R). The study of reduced-size PTH agonist and antagonist analogues has been the subject of extensive research, for the development of safer and non-parenteral bone anabolic drugs. Recent investigations focusing on the interaction of N-terminal fragments of PTH with PTH1R showed that certain modifications can increase signalling potency in peptides as short as 11 amino acids (e.g. S~3→A~3, N~(10)→Q~(10),L→R~(11)).