1 / 7

ENKEPHALINS

ENKEPHALINS. THE BODY’S PAINKILLERS. Met-Enkephalin H-Tyr-Gly-Gly-Phe-Met-OH. Leu-Enkephalin H-Tyr-Gly-Gly-Phe-Leu-OH. NOTES - ENKEPHALINS Endogenous peptides acting as neurotransmitters in brain Enkephalin - Greek for ‘in the head’ Bind to delta receptor ( d )

wyatt
Download Presentation

ENKEPHALINS

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. ENKEPHALINS THE BODY’S PAINKILLERS

  2. Met-Enkephalin H-Tyr-Gly-Gly-Phe-Met-OH Leu-Enkephalin H-Tyr-Gly-Gly-Phe-Leu-OH

  3. NOTES - ENKEPHALINS Endogenous peptides acting as neurotransmitters in brain Enkephalin - Greek for ‘in the head’ Bind to delta receptor (d) Approximately 15 other endogenous peptides of 5-26 AA’s (endorphins and enkephalins). All contain Met or Leu enkephalin at N-terminus Biosynthesised from three inactive protein precursors (proenkephalin, prodynorphin and pro-opiomelanocortin) Inactived by peptidase enzymes in vivo (orally inactive) - hydrolysed between Tyr and Gly H-Tyr-Gly-Gly-Phe-Met-OH

  4. SAR Tyrosine essential for activity (phenol ring and N) Phenol ring of Tyr thought to be equivalent to phenol ring of morphine Tyr nitrogen thought to be equivalent to morphine amine Aromatic ring of Phe important (additional interaction)

  5. Additional Interaction Phenol Phenol Amine Amine

  6. ANALOGUES AIM To synthesise analogues which are stable to peptidases and which would be orally active STRATEGY Replace non essential amino acids with unnatural AA’s or D-AA’s to make enkephalin unrecognisable to peptidase enzymes

  7. unnatural amino acids unnatural amino acids EXAMPLES H-(L-Tyr)-(D-AA)-Gly-(NMe-L-Phe)-(L-Met)-OH Resistant to peptidase. Orally active (N,N-Diallyl-L-Tyr)-aib-aib-(L-Phe)-(L-Met)-OH aib = a-aminobutyric acid Antagonist to the gamma receptor

More Related