Peptides and Proteins Flashcards
What are the thyroid hormones? How are they produced?
Chiral pool
thyroxine (T4)
tri-iodothyronine (T3)
- T3 is more potent than T4
- are derivatives of tyrosine
T3 is produced by de-iodination outside of the thyroid
- T3 has 3 iodine atoms whereas T4 has 4 iodine atoms
How is thyroxine synthesised from tyrosine?
two tyrosine residues in thyroglobulin (a protein made by the follicular cells of the thyroid gland) have iodine atoms added
they are then linked via an there group through oxidative (radical) coupling
re-instatement in the aromaticity of one of the rings causing detachment of the final molecule
- thyroxine (T4)
How is levothyroxine synthesised?
chiral pool approach
- a synthetic process that employs a member of the chiral pool as a starting material in the synthesis of a target molecule. The chiral centre(s) in the starting material are preserved in the target molecule
= L-tyrosine is the starting material (is chiral) which introduces chirality
What is calcitonin? What is its function?
calcitonin is a peptide produced in the thyroid
- works with the parathyroid hormone (PTH) and 1 alpha 2,5-dihydroxyvitamin D3
regulates calcium balance and born turnover
- can suppress calcium loss from bone and treat bone weakening (opposes PTH action)
How is thyroid axis stimulated?
thyrotropin releasing hormone (TRH) is released from the hypothalamus and acts on the anterior pituitary
TRH stimulates thyroid stimulating hormone release (TSH) from the anterior pituitary
- TRH is a tripeptide with modified C and N termini to protect itself from peptidases
TSH acts on the thyroid to stimulate thyroxine release
How are luteinising hormone releasing agents (LHRH/GnRH) modified to improve activity?
amino acid 6 is replaced with D-amino acid
modification or deletion of amino acid 10
How are analogous peptides produced?
solid phase chemical synthesis
- a solid support or resin is used
- a linker is needed to attach the amino acid to the resin
- suitable protecting groups are needed to direct the reaction
How is growth hormone released?
growth hormone releasing hormone (GHRH) os released from the hypothalamus
GHRH acts on the pituitary gland and stimulates human growth hormone release also known as somatotrophin
What is growth hormone release inhibiting factor (GHRIF)? What does it do?
GHRIF is also known as somatostatin
somatostatin inhibits the release of
- HGH, thyrotropin, insulin and glucagon
