Synthesis, characterization and biodistribution studies of (125)I-radioiodinated di-PEGylated bone targeting salmon calcitonin analogue in healthy rats

Pharmaceutical Research
Yang YangMichael R Doschak

Abstract

The objective of this study was to prepare a bisphosphonate (BP) mediated bone targeting di-PEGylated salmon calcitonin analogue sCT-2(PEG-BP) as a novel bone targeting pharmaceutical. HPLC was used for isolation of sCT-2(PEG-BP) from the reaction mixture, followed by determination of possible PEGylation sites by trypsin digestion. Stability of the compound over time, bone mineral affinity using hydroxyapatite, and biodistribution in normal rats after radiolabeling of sCT-2(PEG-BP) or control sCT with (125)I was evaluated. PEGylated sCT analogues were synthesized, and sCT-2(PEG-BP) was isolated by HPLC and confirmed by MALDI-TOF and ICP-MS. MALDI-TOF analysis of trypsinized fragments suggested Cys(1) (or Lys(11)) and Lys(18) to be the two PEGylation sites. Bone mineral affinity test showed sCT-2(PEG-BP) or (125)I-sCT-2(PEG-BP) exhibited significantly increased bone mineral affinity over sCT or (125)I-sCT, respectively. sCT-2(PEG-BP) remained stable for at least 1 month. In vivo biodistribution study showed significantly increased bone retention and prolonged plasma circulation time for sCT-2(PEG-BP) compared to the control sCT. Those results support sCT-2(PEG-BP) as a promising new drug candidate for the treatment of resorptive...Continue Reading

References

Nov 1, 1992·Pharmaceutical Research·K C LeeP P DeLuca
Feb 5, 1991·Biopolymers·J P MeyerV Saudek
Oct 1, 1987·The Journal of Clinical Endocrinology and Metabolism·L SilvestroniL Gnessi
Nov 14, 1997·Drugs & Aging·H M Lamb, D Faulds
Apr 8, 2000·Biotechnology Progress·H UludagD Kantoci
Sep 1, 2000·Science·G A Rodan, T J Martin
Jun 5, 2002·Annals of Nuclear Medicine·Yasushi Arano
Oct 26, 2002·Journal of Controlled Release : Official Journal of the Controlled Release Society·Keon-Hyoung SongChang-Koo Shim
Mar 20, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jeff WangWei-Chiang Shen
Sep 18, 2003·Bioconjugate Chemistry·Dong WangJindrich Kopecek
Jan 27, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sinéad M RyanDavid J Brayden
Apr 25, 2009·Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons·Salvatore L RuggieroUNKNOWN American Association of Oral and Maxillofacial Surgeons
Aug 27, 2009·Chemical Communications : Chem Comm·Mathew W JonesDavid M Haddleton
Apr 24, 2010·International Journal of Pharmaceutics·Krishna Hari BhandariMichael R Doschak
Oct 16, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sinéad M RyanDavid J Brayden
Oct 18, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Krishna Hari BhandariMichael R Doschak
Jan 4, 2012·Journal of Biomedical Materials Research. Part a·Guilin WangHasan Uludağ

❮ Previous
Next ❯

Citations

Feb 19, 2015·Pharmaceutical Research·Crystal Sao-Fong CheungJeffrey Baron
Oct 21, 2015·Advanced Drug Delivery Reviews·Lisa E ColeRyan K Roeder
Jun 24, 2017·ACS Applied Materials & Interfaces·Yanpeng LiuJiandong Ding
Jul 3, 2020·Chemical & Pharmaceutical Bulletin·Hidemasa KatsumiAkira Yamamoto
Jun 8, 2017·Drug Delivery and Translational Research·Jacqueline CawthrayKishor Wasan
Jul 20, 2017·Drug Delivery and Translational Research·Yang YangMichael R Doschak
Aug 1, 2020·Current Drug Targets·Malkiet KaurManjinder Singh

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.