Synthetic ACTH-Like Peptide GKVLKKRR, Corresponding to the Fragment 81–88 of Human Pro-Interleukin-1α, Acts as an Antagonist of ACTH Receptor

  • Elena V. Navolotskaya
  • Yulia A. Kovalitskaya
  • Vladimir B. Sadovnikov
  • Yury A. Zolotarev
  • Alexander A. Kolobov
  • Vladimir V. Yurovsky
  • Valery M. Lipkin
Article
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Synthetic adrenocorticotropic hormone (ACTH)-like octapeptide leukocorticotropin (GKVLKKRR), corresponding to the amino acid sequence 81–88 of pro-interleukin-1α, was labeled with tritium (specific activity of 22 Ci/mmol) and was found to bind to rat adrenal cortex membranes with high affinity and specificity (K d = 2.2 ± 0.1 nM). Synthetic 125I-labeled ACTH fragment 11–24 was also obtained (specific activity of 98 Ci/mmol) and shown to bind to ACTH receptor on rat adrenal cortex with high affinity (K d = 1.8 ± 0.1 nM). Unlabeled leukocorticotropin was found to actively replace 125I-labeled ACTH (11–24) in the receptor-ligand complex (K i = 2.0 ± 0.1 nM). Leukocorticotropin at concentration range of 1–1000 nМ did not affect the adenylate cyclase activity in adrenocortical membranes. Thus, leukocorticotropin is an antagonist of ACTH receptor.

Keywords

adrenocorticotropic hormone interleukin-1 peptides receptors adrenal cortex 

Abbreviations

ACTH

adrenocorticotropic hormone

cAMP

cyclic 3′,5′-adenosinmonophosphate

HSCIE

high-temperature solid-state catalytic isotope exchange

LCT

leucorticotropin

pIL-1α

pro-interleukin-1α

PMSF

phenylmethylsulfonyl fluoride

SEM

standard error of the mean

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Notes

Acknowledgment

This work was supported by the Russian Foundation for Basic Research (grant No. 05-04-48060), by the programs Leading Scientific Schools (grant No. 312.2003.4), Molecular and Cellular Biology (chairman V.M. Lipkin), and Naukogrady (grant No. 04-04-97200), and by the International Science and Technology Center (project No. 2615). V.V. Yurovsky is supported by the American Heart Association (grant No. 0555415U).

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Elena V. Navolotskaya
    • 1
  • Yulia A. Kovalitskaya
    • 1
  • Vladimir B. Sadovnikov
    • 1
  • Yury A. Zolotarev
    • 2
  • Alexander A. Kolobov
    • 3
  • Vladimir V. Yurovsky
    • 4
  • Valery M. Lipkin
    • 1
  1. 1.Branch of Shemyakin and Ovchinnikov Institute of Bioorganic ChemistryRussian Academy of SciencesPushchino, Moscow RegionRussia
  2. 2.Institute of Molecular GeneticsRussian Academy of ScienceMoscowRussia
  3. 3.State Research Center for Institute of Highly Pure BiopreparationsMinistry of Health of the Russian FederationSt. PetersburgRussia
  4. 4.Department of NeurosurgeryUniversity of MarylandBaltimoreUSA

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