- Tytuł:
-
Biwalentne ligandy receptorów opioidowych
Bivalent ligands of opioid receptors - Autorzy:
-
Frączak, O.
Olma, A. - Powiązania:
- https://bibliotekanauki.pl/articles/171626.pdf
- Data publikacji:
- 2014
- Wydawca:
- Polskie Towarzystwo Chemiczne
- Tematy:
-
peptydy opioidowe
biwalentne ligandy niepeptydowe
biwalentne ligandy peptydowe
aktywność opioidowa
homobiwalentne ligandy
heterobiwalentne ligandy
opioid peptides
nonpeptide bivalent ligands
peptide bivalent ligands
opioid activity
homobivalent ligands
heterobivalent ligands - Opis:
- Opioids are the oldest drugs know to humanity, which have been and continue to be used for the treatment of chronic pain. Unfortunately they have a large numbers of side effects [1–6]. Three main types of opioid receptors μ (MOR), δ (DOR) and κ (KOR) are known [8]. The ORL1 receptor was classified as the fourth member of opioid receptor family [9]. Opioid receptors can form homodimers and the following heterodimers: DOR-KOR, DOR-MOR and KOR-MOR [13c,d,f, 14]. Specially designed ligands which are able to penetrate the BBB are used to study physiological consequences of opioid receptor homo- and heterodimerization, and as new analgesics. Bivalent ligands are defined as compounds that contain two pharmacophoric units, an appropriately designed spacer to separate and define the two pharmacophores, and a linker unit to connect the pharmacophores, to the spacer (Fig. 1) [16]. The affinity of a ligand to its target depends on its fundamental kinetic association and dissociation rate constants (Scheme 1) [24]. Bivalent ligands interacting with the opioid receptors have been divided into three groups: nonpeptide, peptide- nonpeptide and peptide homo- or heterodimers. Nonpeptide bivalent ligands (4–21, 27–41 and 44–45) containing different pharmacophores (selective opioid agonists or/and antagonists) connected with designed linkers have potent analgesic properties [25–34]. Compound 35 may be useful in the treatment of opioid dependence. Studies of peptide-nonpeptide ligands, which are a combination of “address” segments of endogenous opioid peptides and selective alkaloid ligand (47–50) indicate that peptide part of the analogues can modulate the receptor selectivity of the attached alkaloid pharmacophores [35]. Series of peptide-nonpeptide ligands containing different classes of opioid peptides and fentanyl (52–86) were synthesized and tested for binding affinity to μ and δ opioid receptors [38–40]. Good opioid affinity and antinociceptive activity of some of the obtained bivalent ligands (57, 61, 63) suggesting that a novel class of analgesics can be further developed utilizing this approach. Among homobivalent ligands the most important is biphalin 87 and its analogues (88–124) [41–53]. Analgesic potency of the most active ligand 112 is greater than parent peptide (biphalin) and morphine.
- Źródło:
-
Wiadomości Chemiczne; 2014, 68, 3-4; 233-255
0043-5104
2300-0295 - Pojawia się w:
- Wiadomości Chemiczne
- Dostawca treści:
- Biblioteka Nauki
Artykuł