Leu -enkephalin

Leu-enkephalin, Met-enkephalin [59141-40-11 polypeptide multiple tissues endogenous opiates... 

In the anterior pituitary gland (see Hormones, anteriorpituitaryhormones), both adrenocorticotropic hormones (ACTH) and the endogenous opiate hormone, P-endorphin, are synthesized from a common prohormone (2) (see Opioids,endogenous). In the adrenal medulla, five to seven copies of another opiate hormone, methionine—enkephalin (Met-enkephalin), and one copy of leucine—enkephalin (Leu-enkephalin) are synthesized from each precursor molecule (3). 

Biosynthesis. Three separate genes encode the opioid peptides (see Fig. 1). Enkephalin is derived from preproenkephalin A, which contains six copies of Met-enkephalin and extended peptides, and one copy of Leu-enkephalin (62—66). ( -Endorphin is one of the many products of POMC, and represents the N-terminal 31 amino acids of P-Hpotropin (67,68). Three different dynorphin peptides are derived from the third opioid gene, preproenkephalin B, or preprodynorphin (69). The dynorphin peptides include dynorphin A, dynorphin B, and a-neo-endorphin. 

Evidence soon emerged that the endogenous opioids were peptides rather than simple morphine-like molecules (9). The first direct evidence for endogenous opioids in brain extracts was provided in 1975 when two pentapeptides were purified that differed only in the carboxyl terminal amino acids (10) (Table 1). These peptides were called methionine- (Met-) and leucine- (Leu-) enkephalin, from the Greek term meaning "in the head."... 

At the time of the discovery of Met-enkephalin, its sequence was observed to be identical to that of residues 61—65 contained in the C-fragment of the pituitary hormone p-Hpotropin [12584-99-5] (p-LPH) (see Hormones), first isolated in 1964 (11). In 1976, the isolation of a larger peptide fragment, P-endorphin [60617-12-1] that also displayed opiate-like activity was reported (12). This peptide s 31-amino-acid sequence comprised residues 61—91 of P-LPH. Subsequentiy, another potent opioid peptide, dynorphin [72957-38-17, was isolated from pituitary (13). The first five amino acids (qv) of this 17-amino-acid peptide are identical to the Leu-enkephalin sequence (see Table 1). 

Fig. 1. Structures of two types of opioid agonists where dotted circles surround structural elements common to both compounds (a) Leu-enkephalin and...

Group II consists of the enkephalins which come from the 267-aniino acid piecuisoi pro-enkephalin A [88402-54-4] (Fig. 2). This proteia contains four copies of Met-enkephalin, one copy of Leu-enkephalin, and the extended peptides Met-enkephalin-Arg -Phe (the last Met-enkephalin sequence ia Fig. 2) and Met-enkephalin-Arg -Gly -Leu (the fourth Met-enkephalin sequence ia Fig. 2) (25,26). AH of these products ate formed by trypsin-like cleavage between pairs of basic residues. The extended enkephalin peptides are further cleaved by carboxypeptidase E (27) to form authentic Met-enkephalin. 

Prototypic ligands Morphine Met/leu-enkephalin Ethylketocyclacozine Nociceptin/OFQ... 

R. M.J. Solid-phase syntheses of peptoids using Fmoc-protected N-substituted glycines The synthesis of (retro) peptoids of leu-enkephalin and substance P. Euro. J. Chem. 1998, 4, 1570-1580. 

Figure 25. The adamantane-conjugated [D-Ala2]Leu-enkephalin prodrugs. Taken from Ref. [144] with permission.

Some propeptides produce multiple copies of similar peptides (met-enkephalin and leu-enkephalin act on the same delta opioid receptor). 

Different peptides from the same gene product (met and leu enkephalin, substance P and neurokinin A). The former two act on the same receptor, the delta opioid receptor, whereas the latter act on different receptors, the neurokinin 1 and 2 receptors. Despite this, the receptors for the neurokinins produce the same direction of effect, a slow depolarisation, even though their distribution differs. 

The pentapeptides, met- and leu-enkephalin, have been detected in rat striatum tissue by LCEC at a glassy carbon electrode These peptides can be detected directly... 

Delta receptors are relatively selective for two related penta-peptides, methionine enkephalin and leucine enkephalin (met- and leu-enkephalin), which were isolated from porcine brain (Hughes 1975). Both met- and leu-enkephalin inhibit electrically induced contractions of guinea pig ileum, an effect that mimics those effects seen with opioid drugs, and is naloxone reversible. The enkephalins are processed posttranslational ly from proenkephalin, and secreted from central and peripheral neurons and endocrine cells in the adrenal medulla. 

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