A National Cancer Institute-designated Comprehensive Cancer Center

Make an appointment: 800-826-HOPE

Synthetic and Biopolymer Chemistry Core

Synthetic and Biopolymer Chemistry Core
Director:
David Horne, Ph.D.
626-256-4673, ext. 67310
 
The Synthetic and Biopolymer Chemistry Core (SBCC) has evolved over three decades to its current state where it provides both biopolymer and small-molecule synthetic services to scientists at City of Hope. These services would not be available from commercial sources.

 

The lab was originally established in 1974 under the leadership of Dr. Bruce Kaplan to facilitate the synthesis of enzyme substrates and carbohydrates. The laboratory synthesized the starting materials that were utilized in thepioneering work on solid phase DNA synthesis, which led to the bioengineering of synthetic insulin (Humulin) by Dr. Art Riggs and Dr. Keiichi Itakura.This important pharmaceutical is still being used today worldwide by millions of people with diabetes. With the arrival of Dr. Piotr Swiderski in 1989 the laboratory was able to provide synthetic RNA and DNA/RNA chimeras to theCity of Hoperesearch community. In 1990 there were only three labs making RNA in the US.

 

The general capabilities of the core include the design and synthesis of highly specialized biopolymers, including siRNA-aptamers, DNA-peptide hybrid derivatives, and peptides. The core is capable of handling the synthesis of very complex molecules, as well as the synthesis of small-molecule agonists and antagonists, imaging agents, affinity ligands, nanoparticles, and focused combinatorial libraries. An important new goal of the SBCC is on cancer drug discovery in the area of molecular-targeted therapeutics. These compounds are used for chemical biology, generation of lead compounds for drug discovery, and ultimately optimization of new drugs for preclinical evaluation.

 

The SBCC is capable of handling the synthesis of all structural classes of small to large organic molecules.A unique strength of the SBCC is in total synthesis of natural products and derivatives. State-of-the-art organic synthesis and the use of modern synthetic methodologies are used for the efficient construction of molecular agents and ligands.

 

The SBCC provides an affordable means and knowledge to access chemistry technology that cannot be supported by individual labs. The centralized intellectual and technical resources of the SBCC can assist the researcher in designing and conducting the proper experiment, preparing the appropriate samples for analysis, and analyzing them in the most appropriate manner.The core can assist in correctly interpreting results in conjunction with the PI.Core staff scientists also provide essential technical support for the operation and maintenance of highly specialized instruments, such as nuclear magnetic resonance (NMR) and mass spectroscopy (MS) equipment.

 

SBCC General Capabilities:

 

  • Provide expertise, consultations, and experience in the area of chemical synthesis and designof biopolymers.
 
  • Provide broad expertise in the custom synthesis of essentially any organic-based compound with particular emphasis on complex natural products and developing improved synthetic routes.
 
  • Provide scale-up protocols for pure materials for pre-clinical and clinical investigations.
 
  • Facilitate collaborations among molecular biologists, chemists, structural biologists, pharmacologists and clinicians.
 
  • Support small-molecule drug discovery for chemical biology and cancer therapeutics development.
 
  • Provide synthesis of radiolabeled compounds and biologicals, such as imaging agents and antibody conjugates.
 
  • Facilitate sharing of instruments, methodologies, and chemical insights with project investigators throughout City of Hope Comprehensive Cancer Center.
 
Research reported in this publication included work performed in the Synthetic and Biopolymer Chemistry Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA33572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
 

Equipment

The Synthetic and Biopolymer Chemistry Core (SBCC) equipment is comprehensive in both small and large molecule synthesis capabilities and state-of-the-art spectroscopic instrumentation for structural characterization. In addition, the lab is equipped with in-house custom-built instruments adapted for specialized applications in the area of biopolymer synthesis.
 
Biopolymer Synthesis
The Synthetic and Biopolymer Chemistry Core maintains several nucleic acid and peptide synthesizers that are adapted for both routine andhighly specialized custom syntheses. These include:
 
Two Automated DNA/RNA Synthesizers. These machines are fully adaptable for custom synthesis to include modified bases as well as other non-natural base and sugar analogs.
 
 
Two Semi-Automated Peptide Synthesizers. These are state-of-the-art, in-house designed and built, semi-automated peptide synthesizers. These custom instruments provide much greater mechanical flexibility and efficiency in the coupling processes that allow for the introduction of difficult-to-incorporate modified amino acid derivatives. Long polypeptides containing >100 amino acids have been synthesized on these instruments, which were unachievable by commercial vendors.
   
Waters HPLC Instrumentation. The HPLC system is specifically adapted for purification of small to relatively large amounts of DNA/RNA and peptides.
Small Molecule Synthesis
 
Virtually all of the small molecule projects involve custom synthesis to varying degrees. A full array of state-of-the-art small molecule instrumentation is available for complete structural characterization. These include:
 
Agilent Analytical and Preparatory HPLCs. In addition to the standard features, these instruments possess chiral separation capabilities that enable the purification and resolution of racemic material providing single enantiomers with high purity.
   
Varian High-Field 400 MHz NMR. This instrument is capable of one- and two-dimensional data analysis with cryoprobe capability for added sensitivity. Higher field NMR instrumentation (500 and 600 MHz) also exists on campus when the need for greater magnet strength arises.
   
JEOL AccuTOF™-DART™ Mass Spectrometer. This new MS design is capable of exact mass measurements under atmospheric conditions with no sample preparation and instantaneous detection. The precision of this new instrument is unmatched for the determination of small-molecule molecular mass of virtually all compound classes.
   
FTIR, UV/VIS and Polarimeter. Spectroscopic instrumentation used for the structural identification of organic functional groups, chromophores, and optical rotation measurements, respectively.
 
 

Pricing

Prices and availability vary.
 
For more information, please contact:
 
David Horne, Ph.D., Director
dhorne@coh.org
626-256-4673, ext. 67310.
 
If you are a City of Hope employee, please click here for pricing.
 

Quality Control

The efficient output of high-quality materials by the Synthetic and Biopolymer Chemistry Core (SBCC) is second to none. The high caliber of scientific core staff members and years of experience ensures efficiency, accuracy, and product reliability. The SBCC is in a unique position to fulfill not only “routine” requests but also deliver novel and custom chemical entities. All materials undergo the utmost stringent purification and structural characterization protocols to ensure high purity and identification. For small molecule work, all compounds are subjected to extensive nuclear magnetic resonance and mass spectroscopy characterization as well as infrared, ultraviolet and combustion analyses. Investigators also receive valuable design and execution input from the SBCC scientists. These discussions often result in the development of better alternatives that are significantly different from the original approach.
 
The Synthetic and Biopolymer Chemistry Core has implemented a series of informatics programs and standard operating procedures (SOP) to ensure proper management of information and data it handles regularly. These steps will also allow for efficient information exchange between the core, its users as well as other Cancer Center cores and shared resources on campus.
 
  • LIMS: The SBCC has in place a comprehensive centralized database, built upon a Laboratory Information Management System (LIMS).
 
  • Information Tracking: eNotebook records daily experiments
 
  • Compound Registration: All compounds including biopolymers, regardless of source, are entered into the database and assigned a unique ID #. The unique ID# facilitates tracking of the compound as it passes through various reactions, assays, and analysis. In addition, chemical properties, source (including link to eNotebook) and structural data are linked to the ID # and are readily accessible.
 
  • Barcoding: Reagents and chemicals have barcode identification for inventory purposes that greatly facilitates ETS compliance.
 
  • Quality Control: All spectral data such as 1H and 13C NMR, mass spec, IR, UV, and HPLC traces are stringently analyzed and deposited in the LIMS for each completed and approved compound.
 

Scientific Accomplishments

Since its inception, the original DNA/RNA and Peptide Synthesis Core has had significant impact on the successful execution and completion of a number of research projects. This core has a long history of scientific achievement and innovation. Dr. Kaplan and co-workers were among the early developers and users of automated DNA and peptide synthesis, having designed and built early prototypes upon which current commercial instruments are based.
 
The biopolymer synthesislaboratory provides a variety of custom oligonucleotides to the research community of City of Hope Comprehensive Cancer Center. The DNA and RNA may be synthesized with many reagents containing modified bases and sugars. In addition, a variety of labels and linkers can be incorporated into the oligomer. Some of the reagents are commercially available but some have to be synthesized in our laboratory. In addition, the facility has produced synthetic reagents that allows for the introduction of cis and 6-4 TT photodimers into an oligonucleotide. The biopolymer lab is capable of synthesizing peptides in excess of 100 amino acids. The laboratory has successfully synthesized peptides with phospho-Thr and -Ser, as well as peptides with biotin and acroyl groups attached to the amino terminus.
 
The facility has recently added the production of fluorescently-labeled peptides to its repertoire and has pioneered the synthesis of chimeric DNA/RNA/DNA molecules for use as anti-sense drugs. As a significant portion of these technologies is developed “in-house” to meet a specific research demand, they have been successfully applied to a myriad of City of Hope Comprehensive Cancer Center projects.
 

Services

The SBCC facility is capable of handling the synthesis of all small to large organic molecules as well as biopolymers such as DNA, RNA and peptides.

In each of these areas, the appropriate SBCC co-director will engage the research PI and staff regarding consultation and formulation of the initial design and subsequent execution to ensure the successful completion of the project.
 
State-of-the-art organic synthesis and the use of modern synthetic methodologies are employed for the efficient construction of molecular agents and ligands. The SBCC is committed to advancing collaborative research efforts through creation of a multidisciplinary team approach to chemical biology and drug discovery.
 
The following is a list of specific services and capabilities currently supported by the Synthetic and Biopolymer Chemistry Core facility:
 
  • Synthesis of DNA and RNA Oligonucleotides. This includes synthesis of commercially unavailable reagents such as derivatives of modified and/or labeled nucleosides.
 
  • Synthesis of Biopolymer Conjugates. Examples include specialized covalent and none-covalent (Watson-Crick) conjugates of variousbiopolymers, for example: siRNA-aptamers or DNA-peptide hybrid derivatives.
 
  • Synthesis of Custom Peptides. Examples include peptides containing phosphorylated serine/threonine/tyrosine residues, acetylated lysines, as well as biotin, fluorescein, D-amino acids, 13C and 15N labeled amino acids and other unusual moieties.
 
  • Development of Novel Purification Techniques. This is particularly applicable for the production and isolation of large amounts of very pure RNA and DNA.Examples include chimeric ribozymes andsiRNAsmodified with cholesterol, which are used in animal studies, as well as large amounts of DNA for NMR structural studies.
 
  • Design and Synthesis of All Small Molecule Structural Classes. This encompasses natural and non-natural analogs of carbocycles, heterocycles, carbohydrates, terpenoids, steroids, small peptides, and peptide mimetics as well as nanoparticle derivatives.
 
  • Design and Execute SAR Studies for Lead Optimization. This is accomplished in close collaboration with the HTS Core and structural biophysical groups in the City of Hope Cancer Center that include NMR, X-ray, and molecular modeling.
 
  • Isolation and Structural Identification of Bioactive Natural Products and Drug Metabolites. An international collaborative effort is underway in conjunction with the Strathclyde Institute (Scotland, UK) to identify anti-cancer natural products from terrestrial sources around the world (vida infra).
 
  • Design and Scale-up Synthesis. Full in-house capabilities are in place for scale-up synthesis of optimized lead candidates for use in chemical biology studies and pre-clinical evaluation.
 
  • Design and Synthesis of Radiolabeled Compounds. This will be accomplished in conjunction with the pharmacology group for metabolic identification studies.
 
  • Design and Synthesis of Structural Diversity-Oriented Combinatorial Libraries for HTS. Libraries are used for the identification and optimization of lead compounds.
 
  • Design, Synthesis, and Development of Novel Fluorescent-Based Substrates for Enzymatic Assays. The objective is to work in close collaboration with biologists toward new and improved enzyme/protein assay development yielding more efficient, accurate, and reliable results.
 
  • Design, Synthesis, and Development of Novel Metal Chelator-Antibody Bioconjugates and Ligands for Use in Tumor Imaging. This includes the design and synthesis of new ligands and thesynthesisof radiolabeled substrates in conjunction with cancer immunotherapeutics researchers.
 
Research Shared Services

City of Hope embodies the spirit of scientific collaboration by sharing services and core facilities with colleagues here and around the world.
 

Recognized nationwide for its innovative biomedical research, City of Hope's Beckman Research Institute is home to some of the most tenacious and creative minds in science.
City of Hope is one of only 41 Comprehensive Cancer Centers in the country, the highest designation awarded by the National Cancer Institute to institutions that lead the way in cancer research, treatment, prevention and professional education.
Learn more about City of Hope's institutional distinctions, breakthrough innovations and collaborations.
Support Our Research
By giving to City of Hope, you support breakthrough discoveries in laboratory research that translate into lifesaving treatments for patients with cancer and other serious diseases.
 
 
 
 
Media Inquiries/Social Media

For media inquiries contact:

Dominique Grignetti
800-888-5323
dgrignetti@coh.org

 

For sponsorships inquiries please contact:

Stefanie Sprester
213-241-7160
ssprester@coh.org

Christine Nassr
213-241-7112
cnassr@coh.org

 
CONNECT WITH US
Facebook  Twitter  YouTube  Blog
 
NEWS & UPDATES
  • Radiology is one of the cornerstones of any hospital. It is a key diagnostic branch of medicine essential for the initial diagnosis of many diseases and has an important role in monitoring a patient’s treatment and predicting outcome. Radiology is the specialty considered to be both the “eyes” and “ears” of med...
  • Donating blood and platelets saves lives. We all know this. Yet every summer, potential blood donors become distracted by vacations and schedule changes. As a result, blood donations fall dramatically across the nation, leaving hospitals frantically trying to bring in much-needed blood for their patients. Earli...
  • To be a great cancer hospital, you need a great oncology program. Just ask City of Hope – and Becker’s Hospital Review. The health care publishing industry stalwart, described as the “leading hospital magazine for hospital business news and analysis for hospital and health system executives,” recently selected ...
  • Diagnostic errors are far from uncommon. In fact, a recent study found that they affect about 12 million people, or 1 in 20 patients,  in the U.S. each year. With cancer, those errors in diagnosis can have a profound impact. A missed or delayed diagnosis can make the disease that much harder to treat, as the Ag...
  • Eleven years ago, lymphoma patient Christine Pechera began the long road toward a cancer-free life. She had been diagnosed with non-Hodgkin lymphoma and told by doctors elsewhere that her lifespan likely would be measured in months, not years. Refusing to give up, she came to City of Hope for a second opinion. ...
  • Brain surgery is not for the faint of heart. It takes courage, as well as curiosity and compassion. The truly great surgeons also have a desire to find new, and better ways, of healing the brain. Enter Behnam Badie, M.D., chief of neurosurgery at City of Hope. Now a pioneer in brain tumor treatment, Badie enter...
  • Elizabeth Budde, M.D., Ph.D., wants to encourage infighting. She aims to turn the immune system on itself — to the benefit of patients with acute myeloid leukemia, or AML. AML arises when abnormal white blood cells grow out of control, amassing in the bone marrow and interfering with normal blood cell developme...
  • Six, to date; more soon. Outpatient bone marrow transplants, that is. Finding new ways to deliver quality care with the greatest benefit is a priority for a patient-centered institution like City of Hope. For example, not every bone marrow transplant patient needs to check into the hospital for treatment. In fa...
  • The best measure of success in the fight against cancer is in lives saved and families intact, in extra days made special simply because they exist. Yuman Fong, M.D., chair of the Department of Surgery at City of Hope, understands what precedes that special awareness. When cancer strikes, one minute a person ma...
  • In cancer, expertise matters. So do survival rates, patient safety, patient services and many other factors. City of Hope understands this, as does U.S.News & World Report. The magazine’s 2014-2015 list of best hospitals for cancer once again includes City of Hope, ranking the institution 12 out of 900 elig...
  • At 29, Kommah McDowell was a successful young professional engaged to be married to her best friend. She worked in the financial services sector and kick-boxed to keep in shape and to relax. Then came the diagnosis of triple-negative inflammatory breast cancer, a rare and very aggressive form of breast cancer. ...
  • The well-known drug tamoxifen might not always be the best choice for premenopausal women who have undergone treatment for breast cancer and face a heightened risk of recurrence. A new study suggests that the aromatase inhibitor exemestane, or Aromasin, works slightly better than tamoxifen in preventing cancer ...
  • At age 44, Bridget Hanchette, a mother of three from La Crosse, Wisconsin, was diagnosed with grade IV glioblastoma, the most aggressive type of malignant brain tumor. The cancer grows and spreads quickly, making it difficult to treat. Most patients with this diagnosis are not given much hope, but Hanchette’s i...
  • Survival rates for childhood cancer have improved tremendously over the past few decades, but postcancer care hasn’t always kept up. More children than ever are now coping with long-term complications and side effects caused by their disease and treatment — one of those being learning difficulties. A new ...
  • When Sheldon Querido, a retired manufacturer’s representative, was diagnosed with bladder cancer, his doctor told him that he’d need to have his bladder removed – and that he’d have to wear an external urine-collection bag for the rest of his life. “My first response was ‘I donR...