Coding

Part:BBa_K200013

Designed by: James Field   Group: iGEM09_Imperial College London   (2009-10-13)

Opiorphin + EK cleavage site

Usage and Biology

Background

Opiorphin is a pentapeptide (five amino acids long) that was isolated from human saliva in 1996. Opiorphin acts as a pain killing agent. The amino acid sequence for opiorphin is Glutamine-Arginine-Phenylalanine-Serine-Arginine.

A combination of opiorphin's potency and natural presence in saliva have sparked a great deal of interest from a number of philosophical movements most notably from [http://en.wikipedia.org/wiki/David_Pearce_(philosopher) David Pearce] who belongs to the [http://en.wikipedia.org/wiki/Utilitarianism#Negative negative utilitarian] school of ethics.

Mechanism of Action

Preliminary rat studies indicate that opiorphin has a pain killing effect six times stronger than that of morphine. Enkephalins which are natural pain-killing opioids, opiorphin inhibits two enkephalin-catabolizing ectoenzymes, human neutral ecto-endopeptidase, hNEP ([http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/enzymes/GetPage.pl?ec_number=3.4.24.11 EC 3.4.24.11]), and human ecto-aminopeptidase, hAP-N ([http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/enzymes/GetPage.pl?ec_number=3.4.11.2 EC 3.4.11.2]). This results in accumulated levels of enkephalins which results in a drop in pain perception 3.

EK Cleavage

See Design Notes for our rationale behind incorporating an EK cleavage sequence on the N terminus of the opiorphin pentapeptide.

Other Side Effects

Priapism:

A recent study involved genetically engineering retired breeder rats to constitutively express opiorphin. Interestingly, this resulted in the development of a priapic-like condition. It is thought that this condition resulted from the upregulation of the ornithine decarboxylase gene (ODC) by opiorphin 1.


Antidiarrheal:

In an in-vitro bioassay it was shown that opiorphin (in concentarions 10−6 to 10−4 M) caused colonic contraction in a concentration-dependent manner 2. Based on this evidence, opiorphin could have potential as an antidiarrheal agent.



Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    COMPATIBLE WITH RFC[21]
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    COMPATIBLE WITH RFC[1000]



References

<biblio>

  1. 1 pmid=19657052
  1. 2 pmid=19442408
  1. 3 pmid=17101991

</biblio>

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