SYNTHESIS OF POTENT ANTAGONISTS FOR THE NATRIURETIC PEPTIDE CLEARANCE RECEPTOR

Elaref Ratemi

doi:10.22159/ajpcr.2017.v10i11.20146

Authors

Elaref Ratemi Jubail Industrial College

DOI:

https://doi.org/10.22159/ajpcr.2017.v10i11.20146

Keywords:

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

Abstract

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.

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Author Biography

Elaref Ratemi, Jubail Industrial College

Department of Chemical and Process Engineering Technology

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