Probing the Bimolecular Interactions of Parathyroid Hormone with the Human Parathyroid Hormone/Parathyroid Hormone-Related Protein Receptor

Orthopedic Spine Surgeon Dr. Kingsley R. Chin Medical Paper

Scientific Paper

Nakamoto C1Behar VChin KRAdams AESuva LJRosenblatt MChorev M.

Interested medical professionals can read through the full paper, also published in Biochemistry, here.

Abstract

Parathyroid hormone (PTH) regulates calcium and phosphate metabolism through a G-protein-coupled receptor which is shared with PTH-related protein (PTHrP). Therefore, structure-activity studies of PTH and PTHrP with their common receptor provide an unusual opportunity to examine the structural elements in the two hormones and their common receptor which are involved in the expression of biological activity. Our approach to studying the nature of the bimolecular interface between hormone and receptor is to use a series of specially designed photoreactive benzophenone- (BP-) containing PTH analogs in “photoaffinity scanning” of the PTH/PTHrP receptor. In this report we describe a series of BP-containing agonists and antagonists which have been synthesized by solid-phase methodology and characterized physiocochemically and biologically. Each of the 12 analogs contains a single BP moiety at a different defined position. Examples of BP-containing agonists prepared and studied in human osteogenic sarcoma Saos-2/B-10 cells are [Nle8,18,Lys13(epsilon-pBZ2),L-2-Nal23,Tyr34]bPTH(1-34 )NH2(K13)(Kb = 13 nM; Km = 2.7 nM) and [Nle8,18,L-Bpa23,Tyr34[bPTH(1-34)NH2(L-Bpa23) (Kb = 42 nM; Km = 8.5 nM). Another BP-containing analog, [Nle8,18,D-2-Nal12,Lys13(epsilon-pBZ2),L-2-Nal23 ,Tyr34]bPTH(7-34)NH2, was a potent antagonist (Kb = 95 nM; Ki = 72 nM). The amino acids substituted by residues carrying the BP moiety span the biologically active domain of the hormone (Phe7, Gly12, Lys13, Trp23, and Lys26). Analysis of photo-cross-linked conjugates of PTH/PTHrP receptor with BP-containing PTH analogs should help to identify the “contact points” between ligand and receptor.

About Author Dr. Kingsley R. Chin

Postoperative Cervical Haematoma Complicated by Ipsilateral Carotid Thrombosis and Aphasia After Anterior Cervical Fusion: a Case Report
Dr. Kingsley R. Chin, founder of philosophy and practice of The LES Society and The LESS Institute

Dr. Kingsley R. Chin is a board-certified Harvard-trained orthopedic spine surgeon and professor with copious business and information technology experience. He sees a niche opportunity where medicine, business and information technology meet and is uniquely experienced at the intersection of these three professions. He currently serves as Professor of Clinical and Biomedical Sciences at the Charles E. Schmidt School of Medicine at Florida Atlantic University and Professor of Clinical Orthopaedic Surgery at the Herbert Wertheim College of Medicine at Florida International University and has experience as Assistant Professor of Orthopaedics at the University of Pennsylvania Medical School and Visiting Professor at the University of the West Indies.

Learn more about Dr. Chin here and connect via LinkedIn.

About Less Exposure Surgery

Less Exposure Surgery (LES) is based on a new philosophy of performing surgery, leading the charge to prove through bench and clinical outcomes research that LES treatment options are the best solutions – to lowering the cost of healthcare, improving outcomes and increasing patient satisfaction. Learn more at LESSociety.org.

The LES Society philosophy: “Tailor treatment to the individual aiding in the quickest recovery and return to a pain-free lifestyle, using LES® techniques that lessen exposure, preserve unoffending anatomy and utilize new technologies which are safe, easy to adopt and reproducible. These LES®techniques lessen blood loss, surgical time and exposure to radiation and can be safely performed in an outpatient center. Less is more.” – Kingsley R. Chin, MD

About The LESS Institute

The LESS Institute is the world leader center of excellence in Less Exposure Surgery. Our safe, effective outpatient treatments help patients recover quickly, avoid expensive hospital stays and return home to their family the same day. Watch our patient stories, follow us on Facebook and visit TheLESSInstitute.com to learn more.

About SpineFrontier

The above study utilized LES Technology from SpineFrontier – leading provider of LES Technologies and instruments – offering surgeons and patients superior technology and services.

Scientific Paper Author and Citation Details

Authors

Nakamoto C1Behar VChin KRAdams AESuva LJRosenblatt MChorev M.

Author information

  1. Division of Bone and Mineral Metabolism, Harvard-Thorndike Laboratories, Beth Israel Hospital, Boston, Massachusetts, USA.

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