Synthesis and structural studies of new analogues of PTH(1-11) containing Cα-tetra-substituted amino acids in position 8

Amino Acids. 2010 Nov;39(5):1369-79. doi: 10.1007/s00726-010-0591-6. Epub 2010 Apr 30.

Abstract

The N-terminal 1-34 fragment of parathyroid hormone (PTH) is fully active in vitro and in vivo and it can reproduce all biological responses characteristic of the native intact PTH. Recently, analogues of PTH(1-11) fragments with helicity-enhancing substitutions have been demonstrated to yield potent analogues of PTH(1-34). The work describes the synthesis, biological activity and structure of analogues of the best modified PTH sequence H-Aib-Val-Aib-Glu-Ile-Gln-Leu-Nle-His-Gln-Har-NH2 (I). In particular, the effect of the Ala/Aib substitution at positions 1 and 3 as well as of the replacement of Nle in position 8 with D-Nle, L-(αMe)-Nle and D-(αMe)-Nle was studied. The resulting peptides were characterized structurally by CD spectroscopy, solution NMR and MD, and in vitro for activity with respect to the cognate receptor, parathyroid hormone receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry*
  • Cells, Cultured
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Parathyroid Hormone / chemical synthesis*
  • Parathyroid Hormone / chemistry*
  • Peptide Fragments / chemical synthesis*
  • Peptide Fragments / chemistry*
  • Stereoisomerism

Substances

  • Amino Acids
  • Parathyroid Hormone
  • Peptide Fragments
  • parathyroid hormone (1-11)