• Elaref Ratemi Jubail Industrial College


Objectives: The objective of this research was to design and prepare natriuretic peptide clearance receptor (NPR-C) clearance receptor antagonists with potential therapy for achondroplasia, an autosomal dominant disorder that interferes with the synthesis of the cartilage growth plate of long bones.

Methods: Peptides were synthesized by the standard solid-phase peptide synthesis (SPPS) protocol on Rink resin using the N-Fmoc/t-butyl protection methodology. Biological activity of NPR-C antagonists was assessed using ATDC5 cells.

Results: SPPS rapidly generated many crude compounds with purities exceeding 80%. The synthesized ligands were further purified by liquid chromatography-mass spectrometry (LC-MS), and their identities were confirmed by MS and nuclear magnetic resonance. Ligands with nanomolar potencies were obtained.

Conclusion: Structure-activity relationship studies resulted in a good selection of stable, low nanomolar, and linear NPR-C antagonists.

Keywords: Natriuretic peptides, Clearance receptor, Achondroplasia, Osteocrin, Structure-activity relationship, Antagonists.

Author Biography

Elaref Ratemi, Jubail Industrial College
Department of Chemical and Process Engineering Technology


1. Vasile VC, Jaffe AS. Natriuretic peptides and analytical barriers. Clin Chem 2017;63:50-8.
2. Baxter GF. The natriuretic peptides. Basic Res Cardiol 2004;99(2):71-5.
3. Rose RA, Giles WR. Natriuretic peptide C receptor signalling in the heart and vasculature. J Physiol 2008;586(2):353-66.
4. Thomas G, Moffatt P, Salois P, Gaumond MH, Gingras R, Godin E, et al. Osteocrin, a novel bone-specific secreted protein that modulates the osteoblast phenotype. J Biol Chem 2003;278(50):50563-71.
5. Yasoda A, Komatsu Y, Chusho H, Miyazawa T, Ozasa A, Miura M, et al. Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway. Nat Med 2004;10(1):80-6.
6. Bartels CF, Bükülmez H, Padayatti P, Rhee DK, van Ravenswaaij- Arts C, Pauli RM, et al. Mutations in the transmembrane natriuretic peptide receptor NPR-B impair skeletal growth and cause acromesomelic dysplasia, type Maroteaux. Am J Hum Genet 2004;75(1):27-34.
7. Amblard M, Fehrentz JA, Martinez J, Subra G. Methods and protocols of modern solid phase Peptide synthesis. Mol Biotechnol 2006;33(3):239-54.
8. Behrendt R, White P, Offer J. Advances in Fmoc solid-phase peptide synthesis. J Pept Sci 2015;22:4-27.
9. Saxena R, Manjan MJ. A thermally responsive short elastin like polypeptide-drug conjugate: Synthesis, characterization and biological evaluation for targeted delivery of anticancer drugs. Int J Pharm Pharm Sci 2014;6:326-33.
10. Anbarasi G, Kumar SK, Narmadha P, Srinivasan N. Effect of Vitamin C on mRNA expression of bmps during fracture healing in the femur callus of Sprague-Dawley female rats. Int J Pharm Pharm Sci 2014;6:208-12.
11. Freidinger RM. Synthesis of γ-lactam-constrained tryptophyllysine
derivatives. J Org Chem 1985;50:3631-3.
12. Wolfe MS, Dutta D, Aubé J. Stereoselective synthesis of freidinger lactams Using oxaziridines derived from amino acids. J Org Chem 1997;62(3):654-63.
13. Veale CA, Alford VC, Aharony D, Banville DL, Bialecki RA, Brown FJ, et al. The discovery of non-basic atrial natriuretic peptide clearance receptor antagonists. Part 1. Bioorg Med Chem Lett 2000;10(17):1949-52.
293 Views | 250 Downloads
How to Cite
Ratemi, E. “SYNTHESIS OF POTENT ANTAGONISTS FOR THE NATRIURETIC PEPTIDE CLEARANCE RECEPTOR”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 10, no. 11, Nov. 2017, pp. 387-91, doi:10.22159/ajpcr.2017.v10i11.20146.
Original Article(s)