The major goal of this Core Facility, which was recently completely renovated for this use by the University of Arizona, are to synthesize 200 mg to 2.0 gram quantities of biologically active peptides that are needed for extensive biochemical, pharmacological, biological and biophysical studies in this Program Project. Of particular importance will be the development of proper synthetic, purification, and analytical methodologies that are needed for obtaining permission from the FDA to go into clinical trials.
The specific aims of the Core Facility are: 1. To prepare gram quantities of DPDPE and [p-C1Phe4]DPDPE in a form suitable for final toxicity studies in animals, and to do all the necessary synthetic, purification and analytical methodology so that an application for clinical trials can be filed with the FDA. 2. To prepare gram quantities of [D-Tca1]CTAP and biphalin and their analogues for extensive biochemical, pharmacological and biophysical studies including bioavailability and degradation studies. 3. To prepare gram quantities of the deltorphins and carefully selected biostable analogues for extensive biochemical, pharmacological and biophysical studies including bioavailability and degradation studies. 4. To prepare 100-300 mg quantities of any peptide analogue or mimetic that appears to have promising qualities following comprehensive screens done in our Biochemical Core. 5. To prepare peptides (in the quantities needed for the Program Project) that are not available commercially or too expensive including mu receptor inhibitors such as CTAP and kappa receptor agonists. 6. To develop separation methods and other analytical methodology for large-scale synthesis of desired peptides and as needed for preparation of an application for clinical trials to the FDA. 7. To prepare 100 mg to 1 g quantities of any new compounds or conjugates that cross the blood-brain barrier more effectively for further comprehensive studies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Program Projects (P01)
Project #
5P01DA006284-06
Application #
3753002
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Arizona
Department
Type
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Remesic, Michael; Macedonio, Giorgia; Mollica, Adriano et al. (2018) Cyclic biphalin analogues with a novel linker lead to potent agonist activities at mu, delta, and kappa opioid receptors. Bioorg Med Chem 26:3664-3667
Mowlazadeh Haghighi, Saghar; Zhou, Yang; Dai, Jixun et al. (2018) Replacement of Arg with Nle and modified D-Phe in the core sequence of MSHs, Ac-His-D-Phe-Arg-Trp-NH2, leads to hMC1R selectivity and pigmentation. Eur J Med Chem 151:815-823
Sandweiss, A J; McIntosh, M I; Moutal, A et al. (2018) Genetic and pharmacological antagonism of NK1 receptor prevents opiate abuse potential. Mol Psychiatry 23:1745-1755
Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita et al. (2017) Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain. Pain 158:2386-2395
Vardanyan, Ruben S; Cain, James P; Haghighi, Saghar Mowlazadeh et al. (2017) Synthesis and Investigation of Mixed ?-Opioid and ?-Opioid Agonists as Possible Bivalent Ligands for Treatment of Pain. J Heterocycl Chem 54:1228-1235
Cai, Minying; Marelli, Udaya Kiran; Mertz, Blake et al. (2017) Structural Insights into Selective Ligand-Receptor Interactions Leading to Receptor Inactivation Utilizing Selective Melanocortin 3 Receptor Antagonists. Biochemistry 56:4201-4209
Remesic, Michael; Lee, Yeon Sun; Hruby, Victor J (2016) Cyclic Opioid Peptides. Curr Med Chem 23:1288-303
Ramos-Colon, Cyf N; Lee, Yeon Sun; Remesic, Michael et al. (2016) Structure-Activity Relationships of [des-Arg7]Dynorphin A Analogues at the ? Opioid Receptor. J Med Chem 59:10291-10298
Hall, Sara M; Lee, Yeon Sun; Hruby, Victor J (2016) Dynorphin A analogs for the treatment of chronic neuropathic pain. Future Med Chem 8:165-77
Deekonda, Srinivas; Cole, Jacob; Sunna, Sydney et al. (2016) Enkephalin analogues with N-phenyl-N-(piperidin-2-ylmethyl)propionamide derivatives: Synthesis and biological evaluations. Bioorg Med Chem Lett 26:222-7

Showing the most recent 10 out of 268 publications