CCPA (biochemistry)

{{Other uses|CCPA (disambiguation){{!}}CCPA}}{{Chembox

| verifiedrevid = 403603722

| Name = CCPA

| ImageFile = 2-Chloro-N(6)cyclopentyladenosine.svg

| ImageSize = 250px

| IUPACName = 2-Chloro-N⁶-cyclopentyladenosine

| SystematicName = (2R,3R,4S,5R)-2-[2-Chloro-6-(cyclopentylamino)-9H-purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol

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|Section1={{Chembox Identifiers

| Abbreviations = CCPA

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 110356

| InChIKey = XSMYYYQVWPZWIZ-IDTAVKCVBF

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| StdInChI = 1S/C15H20ClN5O4/c16-15-19-12(18-7-3-1-2-4-7)9-13(20-15)21(6-17-9)14-11(24)10(23)8(5-22)25-14/h6-8,10-11,14,22-24H,1-5H2,(H,18,19,20)/t8-,10-,11-,14-/m1/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = XSMYYYQVWPZWIZ-IDTAVKCVSA-N

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| CASNo = 37739-05-2

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| ChEMBL = 284969

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| PubChem = 123807

| IUPHAR_ligand = 374

| SMILES = Clc1nc(c2ncn(c2n1)[C@@H]3O[C@@H]([C@@H](O)[C@H]3O)CO)NC4CCCC4

| InChI = 1/C15H20ClN5O4/c16-15-19-12(18-7-3-1-2-4-7)9-13(20-15)21(6-17-9)14-11(24)10(23)8(5-22)25-14/h6-8,10-11,14,22-24H,1-5H2,(H,18,19,20)/t8-,10-,11-,14-/m1/s1

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| MeSHName = 2-chloro-N(6)cyclopentyladenosine

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|Section2={{Chembox Properties

| Formula = C₁₅H₂₀ClN₅O₄

| MolarMass = 369.80 g/mol

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2-Chloro-N⁶-cyclopentyladenosine (CCPA) is a specific receptor agonist for the Adenosine A1 receptor.{{cite journal|author1=Karl-Norbert Klotz|author2=Martin J. Lohse|author3=Ulrich Schwabe|author4=Gloria Cristalli|author5=Sauro Vittori|author6=Mario Grifantini|title= 2-Chloro-N6-[3H]cyclopentyladenosine ([3HCCPA) — a high affinity agonist radioligand for A1 adenosine receptors|journal= Naunyn-Schmiedeberg's Archives of Pharmacology |volume = 340 |year = 1989 |issue=6 |pages = 679–683 |doi = 10.1007/BF00717744 |pmid=2615857 |s2cid=1114190 }} 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

CCPA is chemically characterized by the addition of a chlorine atom at the 2-position and a cyclopentyl group at the N⁶ position of the adenosine molecule. These modifications enhance its receptor selectivity and binding affinity. The molecular formula of CCPA is C₁₅H₁₉ClN₅O₄, with a molecular weight of approximately 367.80 g/mol.

Pharmacological Profile

= Affinity and Selectivity for Adenosine Receptors =

CCPA exhibits a high binding affinity for A₁ adenosine receptors. In rat brain membranes, it demonstrated a K_i value of 0.4 nM, indicating potent interaction. Its selectivity is underscored by a significantly lower affinity for A_2A receptors, with a K_i value of 3,900 nM, reflecting nearly 10,000-fold selectivity for A₁ over A_2A.{{Cite journal |last1=Gao |first1=Zhan-guo |last2=Jacobson |first2=Kenneth A. |date=May 2002 |title=2-Chloro-N6-cyclopentyladenosine, adenosine A1 receptor agonist, antagonizes the adenosine A3 receptor |journal=European Journal of Pharmacology |language=en |volume=443 |issue=1–3 |pages=39–42 |doi=10.1016/S0014-2999(02)01552-2 |pmc=8358783 |pmid=12044789}}{{Cite journal |last1=Cristalli |first1=Gloria |last2=Volpini |first2=Rosaria |last3=Vittori |first3=Sauro |last4=Camaioni |first4=Emidio |last5=Monopoli |first5=Angela |last6=Conti |first6=Annamaria |last7=Dionisotti |first7=Silvio |last8=Zocchi |first8=Cristina |last9=Ongini |first9=Ennio |date=May 1994 |title=2-Alkynyl Derivatives of Adenosine-5'-N-ethyluronamide: Selective A2 Adenosine Receptor Agonists with Potent Inhibitory Activity on Platelet Aggregation |url=https://doi.org/10.1021/jm00037a024 |journal=Journal of Medicinal Chemistry |volume=37 |issue=11 |pages=1720–1726 |doi=10.1021/jm00037a024 |pmid=8201607 |issn=0022-2623}}

= Functional Effects =

As an A₁ receptor agonist, CCPA effectively inhibits adenylate cyclase activity. In rat adipocyte membranes, it achieved an IC₅₀ of 33 nM, demonstrating its potency. Conversely, its influence on A_2A receptors is minimal, requiring much higher concentrations to elicit comparable effects.

= Interaction with A<nowiki><sub>3</sub></nowiki> Adenosine Receptors =

Interestingly, while CCPA acts as an agonist at A₁ receptors, it functions as a moderate antagonist at human A₃ adenosine receptors. Studies using Chinese hamster ovary cells expressing human A₃ receptors revealed that CCPA binds with a K_i of 38 nM but does not activate the receptor. Instead, it competitively inhibits the effects of A₃ receptor agonists, highlighting its dual role depending on the receptor subtype.{{Cite journal |last1=Lohse |first1=MartinJ. |last2=Klotz |first2=Karl-Norbert |last3=Schwabe |first3=Ulrich |last4=Cristalli |first4=Gloria |last5=Vittori |first5=Sauro |last6=Grifantini |first6=Mario |date=June 1988 |title=2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1 adenosine receptors |url=http://link.springer.com/10.1007/BF00175797 |journal=Naunyn-Schmiedeberg's Archives of Pharmacology |language=en |volume=337 |issue=6 |doi=10.1007/BF00175797 |issn=0028-1298}}

Applications in Biomedical Research

CCPA's selectivity and efficacy make it an invaluable tool in exploring adenosine receptor functions. In cardiovascular studies, it has been employed to investigate A₁ receptor-mediated cardioprotective mechanisms, including modulation of heart rate and ischemic responses (Ischemia). In neurological contexts, CCPA aids in elucidating the role of A₁ receptors in neurotransmission and neuroprotection. Additionally, its antagonistic properties at A₃ receptors provide insights into the complex interplay between different adenosine receptor subtypes.

2-Chloro-N⁶-cyclopentyladenosine (CCPA) stands out as a potent and selective adenosine A₁ receptor agonist with unique antagonistic effects on A₃ receptors.{{Cite journal |last1=Fabera |first1=Petr |last2=Parizkova |first2=Martina |last3=Uttl |first3=Libor |last4=Vondrakova |first4=Katerina |last5=Kubova |first5=Hana |last6=Tsenov |first6=Grygoriy |last7=Mares |first7=Pavel |date=2019-06-14 |title=Adenosine A1 Receptor Agonist 2-chloro-N6-cyclopentyladenosine and Hippocampal Excitability During Brain Development in Rats |journal=Frontiers in Pharmacology |volume=10 |page=656 |doi=10.3389/fphar.2019.00656 |doi-access=free |issn=1663-9812 |pmc=6587156 |pmid=31258477}} 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

Category:Nucleosides

Category:Purines

Category:Organochlorides

Category:Adenosine receptor agonists

Category:Cyclopentyl compounds