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CCPA (biochemistry)
From Wikipedia - Reading time: 9 min
cyclopentyladenosine.svg) | |
| Names | |
|---|---|
| IUPAC name
2-Chloro-N6-cyclopentyladenosine
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| Systematic IUPAC name
(2R,3R,4S,5R)-2-[2-Chloro-6-(cyclopentylamino)-9H-purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol | |
| Identifiers | |
3D model (JSmol)
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| Abbreviations | CCPA |
| ChEMBL | |
| ChemSpider | |
| MeSH | 2-chloro-N(6)cyclopentyladenosine |
PubChem CID
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CompTox Dashboard (EPA)
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| Properties | |
| C15H20ClN5O4 | |
| Molar mass | 369.80 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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2-Chloro-N6-cyclopentyladenosine (CCPA) is a specific receptor agonist for the Adenosine A1 receptor.[1] It is similar to N6-cyclopentyladenosine. Initially developed to probe the physiological and pharmacological roles of adenosine receptors, CCPA has become a pivotal tool in cardiovascular and neurological research. Due to CCPA's high affinity for Adenosine A1 receptors, its tritiated derivative [3H]CCPA can be used as a diagnostic tool for detecting the receptors in tissue with low receptor density.
Chemical Structure and Properties
[edit]CCPA is chemically characterized by the addition of a chlorine atom at the 2-position and a cyclopentyl group at the N<sup>6</sup> position of the adenosine molecule. These modifications enhance its receptor selectivity and binding affinity. The molecular formula of CCPA is C<sub>15</sub>H<sub>19</sub>ClN<sub>5</sub>O<sub>4</sub>, with a molecular weight of approximately 367.80 g/mol.
Pharmacological Profile
[edit]Affinity and Selectivity for Adenosine Receptors
[edit]CCPA exhibits a high binding affinity for A<sub>1</sub> adenosine receptors. In rat brain membranes, it demonstrated a K<sub>i</sub> value of 0.4 nM, indicating potent interaction. Its selectivity is underscored by a significantly lower affinity for A<sub>2A</sub> receptors, with a K<sub>i</sub> value of 3,900 nM, reflecting nearly 10,000-fold selectivity for A<sub>1</sub> over A<sub>2A</sub>.[2][3]
Functional Effects
[edit]As an A<sub>1</sub> receptor agonist, CCPA effectively inhibits adenylate cyclase activity. In rat adipocyte membranes, it achieved an IC<sub>50</sub> of 33 nM, demonstrating its potency. Conversely, its influence on A<sub>2A</sub> receptors is minimal, requiring much higher concentrations to elicit comparable effects.
Interaction with A<sub>3</sub> Adenosine Receptors
[edit]Interestingly, while CCPA acts as an agonist at A<sub>1</sub> receptors, it functions as a moderate antagonist at human A<sub>3</sub> adenosine receptors. Studies using Chinese hamster ovary cells expressing human A<sub>3</sub> receptors revealed that CCPA binds with a K<sub>i</sub> of 38 nM but does not activate the receptor. Instead, it competitively inhibits the effects of A<sub>3</sub> receptor agonists, highlighting its dual role depending on the receptor subtype.[2][4]
Applications in Biomedical Research
[edit]CCPA's selectivity and efficacy make it an invaluable tool in exploring adenosine receptor functions. In cardiovascular studies, it has been employed to investigate A<sub>1</sub> receptor-mediated cardioprotective mechanisms, including modulation of heart rate and ischemic responses (Ischemia). In neurological contexts, CCPA aids in elucidating the role of A<sub>1</sub> receptors in neurotransmission and neuroprotection. Additionally, its antagonistic properties at A<sub>3</sub> receptors provide insights into the complex interplay between different adenosine receptor subtypes.
2-Chloro-N<sup>6</sup>-cyclopentyladenosine (CCPA) stands out as a potent and selective adenosine A<sub>1</sub> receptor agonist with unique antagonistic effects on A<sub>3</sub> receptors.[5] Its distinct chemical structure underpins its receptor specificity, rendering it a crucial compound in cardiovascular and neurological research. Ongoing studies continue to uncover its potential therapeutic applications and deepen our understanding of adenosine receptor pharmacology.
References
[edit]- ^ Karl-Norbert Klotz; Martin J. Lohse; Ulrich Schwabe; Gloria Cristalli; Sauro Vittori; Mario Grifantini (1989). "2-Chloro-N6-[3H]cyclopentyladenosine ([3HCCPA) — a high affinity agonist radioligand for A1 adenosine receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 340 (6): 679–683. doi:10.1007/BF00717744. PMID 2615857. S2CID 1114190.
- ^ a b Gao, Zhan-guo; Jacobson, Kenneth A. (May 2002). "2-Chloro-N6-cyclopentyladenosine, adenosine A1 receptor agonist, antagonizes the adenosine A3 receptor". European Journal of Pharmacology. 443 (1–3): 39–42. doi:10.1016/S0014-2999(02)01552-2. PMC 8358783. PMID 12044789.
- ^ Cristalli, Gloria; Volpini, Rosaria; Vittori, Sauro; Camaioni, Emidio; Monopoli, Angela; Conti, Annamaria; Dionisotti, Silvio; Zocchi, Cristina; Ongini, Ennio (May 1994). "2-Alkynyl Derivatives of Adenosine-5'-N-ethyluronamide: Selective A2 Adenosine Receptor Agonists with Potent Inhibitory Activity on Platelet Aggregation". Journal of Medicinal Chemistry. 37 (11): 1720–1726. doi:10.1021/jm00037a024. ISSN 0022-2623. PMID 8201607.
- ^ Lohse, MartinJ.; Klotz, Karl-Norbert; Schwabe, Ulrich; Cristalli, Gloria; Vittori, Sauro; Grifantini, Mario (June 1988). "2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1 adenosine receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 337 (6). doi:10.1007/BF00175797. ISSN 0028-1298.
- ^ Fabera, Petr; Parizkova, Martina; Uttl, Libor; Vondrakova, Katerina; Kubova, Hana; Tsenov, Grygoriy; Mares, Pavel (2019-06-14). "Adenosine A1 Receptor Agonist 2-chloro-N6-cyclopentyladenosine and Hippocampal Excitability During Brain Development in Rats". Frontiers in Pharmacology. 10: 656. doi:10.3389/fphar.2019.00656. ISSN 1663-9812. PMC 6587156. PMID 31258477.
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