Biomedical Engineering Reference
In-Depth Information
TABLE 19.2
Endogenous Opioid Peptides
Opioid Peptide
Product
Precursor
Amino Acid Sequence
Pro-enkephalin
[Met]-enkephalin
YGGFM
[Leu]-enkephalin
YGGFL
YGGFM
RF
YGGFM
RGL
Peptide E
YGGFM
RRVGRPEWWMDYQKR
YGGFM
BAM 22P
YGGFM
RRVGRPEWWMDYQKRYG
Metorphamide
YGGFM
RRVNH
2
Pro-opiomelanocortin
YGGFM
TSEKSQTPLVTLFKNAIIKNAYKKGE
b-Endorphin
Prodynorphin
Dynorphin A
YGGFL
RRIRPKLKWDNQ
Dynorphin A(1-8)
YGGFL
RRI
Dynorphin B
YGGFL
RRQFKVVT
YGGFL
RKYPK
a-Neoendorphin
YGGFL
RKYP
b-Neoendorphin
Pronociceptin/orphanin-FQ
Nociceptin/orphanin-FQ
FGGFTGARKSARKLANQ
Endomorphin-1
YPWF-NH
2
Endomorphin-2
YPFF-NH
2
Prodermorphin and prodeltorphin
a
Dermorphin
Y(d)AFGYPS-NH
2
Deltorphin
Y(d)MFHLMD-NH
2
Deltorphin I
Y(d)AFDVVG-NH
2
Deltorphin II
Y(d)AFEVVG-NH
2
Note:
The pentapeptide sequences corresponding to [Met]- and [Leu]-enkephalin contained in other opioid peptides
are shown in bold. Note that b-endorphin and most of the opioid peptides derived from proenkephalin contain
[Met]-enkephalin at their N-termini, whereas the sequence of [Leu]-enkephalin is present in those peptides
derived from prodynorphin.
a
Dermorphin and deltorphins are derived from multiple precursors and all have a naturally occurring d-amino acid
in position 2.
•
Chemical modii cation of morphine and related structures (opiates)
•
Simplii cation of the morphine structure
•
Dimerization (bivalent ligands)
•
Peptides and peptidomimetics
The early development was focused on the i rst two approaches. Examples of opiates that display
similar afi nity to all subtypes are shown in the upper part of Figure 19.3. Introduction of bulky sub-
stituents to the morphine structure generally yields antagonists, and naloxone and naltrexone are unse-
lective antagonists.
N
-Allyl analogue nalorphine is an example of a mixed agonist-antagonist. It was
originally characterized as an antagonist, but later shown to have antagonist activity at MOR but ago-
nist activity at KOR. Nalorphine was one of the i rst compounds to be extensively tested in the clinic
in combination with morphine to i nd an ideal agonist-antagonist ratio for maximizing analgesics
properties and minimizing adverse effects. Buprenorphine is a potent analgesic and partial agonist at
the MOR and antagonist at DOR and KOR. Diprenorphine is reported as an unselective antagonist.
An increasing number of subtype selective ligands has been reported and a few examples are
shown in the lower part of Figure 19.3. Compounds that are m-selective include morphine that is
