Interested medical professionals can read through the full paper, also published in Biochemistry, here.
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
Dr. Kingsley R. Chin is a board certified Harvard-trained orthopedic spine surgeon and professor with copious business and information technology exposure. He sees a niche opportunity where medicine, business and info. tech meet – and is uniquely educated at the intersection of these three professions. He has experience as Professor of Clinical Biomedical Sciences & Admissions Committee Member at the Charles E. Schmidt College of Medicine at Florida Atlantic University, Professor of Clinical Orthopedic Surgery at the Herbert Wertheim College of Medicine at Florida International University, Assistant Professor of Orthopaedics at the University of Pennsylvania Medical School, Visiting Spine Surgeon & Professor at the University of the West Indies, Mona, and Adjunct Professor of Clinical Biomedical Studies at the University of Technology, Jamaica.
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
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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
- Division of Bone and Mineral Metabolism, Harvard-Thorndike Laboratories, Beth Israel Hospital, Boston, Massachusetts, USA.