Difference between revisions of "Part:BBa K200014"

 
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<partinfo>BBa_K200014 short</partinfo>
 
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This part codes for the pentapeptide opiorphin. An enterokinase cleavage site and HIS tag have been included for purification purposes.
 
This part codes for the pentapeptide opiorphin. An enterokinase cleavage site and HIS tag have been included for purification purposes.
  
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===Usage and Biology===
 
===Usage and Biology===
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==Background==
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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.
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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.
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==Mechanism of Action==
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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 <sup>3</sup>.
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==EK Cleavage==
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See [https://parts.igem.org/Part:BBa_K200014:Design Design Notes] for our rationale behind incorporating an EK cleavage sequence and HIS tag onto the N terminus of the opiorphin pentapeptide.
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==Other Side Effects==
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<b>Priapism:</b>
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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 <sup>1</sup>.
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<b>Antidiarrheal:</b>
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In an in-vitro bioassay it was shown that opiorphin (in concentarions 10<sup>−6</sup> to 10<sup>−4</sup> M) caused colonic contraction in a concentration-dependent manner <sup>2</sup>. Based on this evidence, opiorphin could have potential as an antidiarrheal agent.
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<partinfo>BBa_K200014 parameters</partinfo>
 
<partinfo>BBa_K200014 parameters</partinfo>
 
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===References===
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<biblio>
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#1 pmid=19657052
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#2 pmid=19442408
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#3 pmid=17101991
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</biblio>

Latest revision as of 15:40, 18 October 2009

Opiorphin + EK cleavage site + His Tag

This part codes for the pentapeptide opiorphin. An enterokinase cleavage site and HIS tag have been included for purification purposes.

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 and HIS tag onto 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>