The University of Toledo

Maurice Manning, Ph.D., D.Sc.

Maurice Manning, Ph.D., D.Sc. Distinguished University Professor  Department of Biochemistry and Cancer Biology Ombudsman, The University of Toledo College of Medicine and Life Sciences maurice.manning@utoledo.edu Curriculum Vitae List of Scientists Who Have Received Peptides as Research Tools 1980-2012

RESEARCH INTERESTS:

Research in my laboratory is focused on the design and solid phase synthesis of peptide ligands for the vasopressin V1a, V1b and V2 receptors and for the oxytocin (OT) receptor (selective agonists and antagonists; radioiodinated and fluorescent ligands).  Many of these peptides have been utilized as research tools in laboratories worldwide and have helped to advance research in the oxytocin vasopressin field. To date, over 3,000 samples of oxytocin and vasopressin agonists and antagonists from this laboratory have been donated to over 700 scientific investigators (some multiple times) for their own independent studies (see list above). Over 2,000 publications from other laboratories have resulted from the use of these peptides over the past 30 years.  My laboratory continues to supply other scientists in the U.S. and throughout the world with samples of vasopressin and oxytocin peptide agonists, antagonists and radioiodinateable ligands for their own independent studies.

Currently these peptide designs are focused on the CNS actions of oxytocin and vasopressin; with the following goals in mind:  (1) the design of (a) long-acting oxytocin agonists and (b) "biased" OT agonists; for use as pharmacological tools and potential therapeutic agents for the study of and treatment of autism spectrum disorders (ASD) and related disorders and (2) the design of selective antagonists, radiolabelled and fluorescent ligands for the human and rat vasopressin V1b receptors; for studies on V1b receptors in the brain and as potential new therapies for anxiety and stress.  The synthetic studies are being carried out in my laboratory by returning visiting scholars from Poland:  Drs. Krzysztof Bankowski, Aleksandra Olma and Aleksandra Misicka.  All three have made imortant contributions to my laboratory in the past.  The resultant peptides, are being pharmacologically characterized by long time collaborators Drs. Gilles Guillon, Maithe Corbani, Thierry Durroux and Bernard Mouillac, Montpellier, France; and by Dr. Bice Chini, Milan, Italy.

Member of the mentoring faculty for the Biomedical Sciences Graduate Program (Cancer Biology Track).

EDUCATION:

B.Sc. 1957 University College Galway, Galway*, Ireland, (1st Honors) Chemistry
M.Sc. 1958 University College Galway, Galway*, Ireland, Chemistry
Ph.D. 1961 University of London, London, England, Organic Chemistry
D.Sc. 1974 University College Galway, Galway*, Ireland, Peptide Chemistry
*Now The National University of Ireland, Galway (NUIG)

ACADEMIC APPOINTMENTS:

1973-Present Professor, Biochemistry & Cancer Biology, University of Toledo College of Medicine,+ Toledo, Ohio
1969 - 1973 Associate Professor, Biochemistry, University of Toledo College of Medicine,+ Toledo, Ohio
1965 - 1969 Assistant Professor, Biochemistry, McGill University, Montreal
1964 - 1965 Research Associate, Rockefeller University, New York
1961 - 1964 Research Associate, Cornell University Medical College, New York
+Formerly The Medical College of Ohio (1964-2005) and the Medical University of Ohio (2005-2006)

REPRESENTATIVE PUBLICATIONS:

L.L. Cheng, S. Stoev, M. Manning, S. Derick, A. Pena, M. Ben Mimoun and G. Guillon (2004) Design of Potent and Selective Agonists for the Human Vasopressin V1b Receptor Based on Modifications of [deamino-Cys1] Arginine Vasopressin at Position 4.  J. Med. Chem. 47:2375-2388.

M. Manning, L.L. Cheng, S. Stoev, N.C. Wo, W.Y. Chan, H.H. Szeto, T. Durroux, B. Mouillac and C. Barberis (2005) Design of Peptide Oxytocin Antagonists with Strikingly Higher Affinities and Selectivities for the Human Oxytocin Receptor than Atosiban.  J. Peptide Sci. 11:593-608.

G.Guillon, A. Pena, B. Murat, S. Derick, M. Trueba, M.A. Ventura, H. Szeto, N. Wo, S. Stoev, L. Cheng and M. Manning (2006) Position 4-Analogues of [Deamino-Cys1] Arginine Vasopressin Exhibit Striking Species Differences for Human and Rat V2/V1b Receptor Selectivity.  J. Peptide Sci. 12:190-198.

A. Pena, B. Murat, M. Trueba, M.A. Ventura, N.C. Wo, H.H. Szeto, L.L. Cheng, S. Stoev, G. Guillon and M. Manning (2007) Design and Synthesis of The First Selective Agonists for the Rat Vasopressin V1b Receptor:  Based on Modifications of deamino-[Cys1]Arginine Vasopressin at Positions 4 and 8.  J. Med. Chem. 50:835-847.

A. Pena, B. Murat, M. Trueba, M.A. Ventura, G. Bertrand, L.L. Cheng, S. Stoev, H.H. Szeto, N. Wo, G. Brossard, C. Serradeil-Le Gal, M. Manning and G. Guillon (2007) Pharmacological and Physiological Characterization of d[Leu4,Lys8]Vasopressin, the First V1b Selective Agonist for Rat Vasopressin/Oxytocin Receptors.  Endocrinology 148:4136-4146.

M. Manning (2008) Impact of the Merrifield Solid Phase Method on the Design and Synthesis of Selective Agonists and Antagonists of Oxytocin and Vasopressin:  A Historical Perspective.  Biopolymers (Peptide Science) 90(3):203-212, 2008.

B. Chini and M. Manning (2007) Agonist Selectivity in the Oxytocin/Vasopressin Receptor Family:  New Insights and Challenges.  Biochem. Soc. Transactions 35 (Pt4):737-741.

M. Manning, S. Stoev, B. Chini, T. Durroux, B. Mouillac and G. Guillon.  Peptide and Nonpeptide Agonists and Antagonists for the Vasopressin and Oxytocin V1a, V1b, V2 and OT Receptors:  Research Tools and Potential Therapeutic Agents.  In Advances in Vasopressin and Oxytocin - from Genes to Behaviour and Disease (eds. Rainer Landgraf and Inga Neumann) Prog. Brain Res. 170:473-512, 2008.

M. Manning.  Peptides versus Non-Peptides.  Invited commentary in The European Peptide Society Newsletter (Ed. Paul Cordopatis).  European Peptide Society:  Issue Number 41: 14, January 2010.  Reprinted in American Peptide Society Newsletter, Spring 2010, page 5.

L. Albizu, M. Cottet, M. Kralikova, S. Stoev, R. Seyer, I. Brabet, T. Roux, H. Bazin, E. Bourrier, L. Lamarque, C. Breton, M.-L. Rives, A.H. Newman, J.A. Javitch, E. Trinquet, M. Manning, J.-P. Pin, B. Mouillac and T. Durroux.  Time-resolved FRET between GPCR ligands reveals oligomers in native tissues.  Nature Chem. Biol. 6:587-594, 2010.

B. Mouillac, M. Manning and T. Durroux.  Fluorescent agonists and antagonists for vasopressin/oxytocin G-protein-coupled receptors: usefulness in ligand screening assays and receptor studies.  Mini Reviews in Medicinal Chemistry 8(10):996-1005, 2008.

M. Manning, S. Stoev and K. Bankowski.  Peptides Versus Non-Peptides as Therapeutics: An Exciting Challenge for Big Pharma. Proceedings of the 31^st European Peptide Symposium (M. Lebl, M. Mendal, K.J. Jensen, T. Hoeg-Jensen (eds.).  European Peptide Society, 366-367, 2010.

M. Corbani, M. Trueba, S. Stoev, B. Murat, J. Mion, V. Boulay, G. Guillon and M. Manning.  Design, Synthesis and Pharmacological Characterization of Fluorescent Peptides for Imaging Human V1b Vasopressin or Oxytocin Receptors.  J. Med. Chem. 54:2864-2877, 2011.

Maurice Manning, Aleksandra Misicka, Aleksandra Olma, Krzysztof Bankowski, Stoytcho Stoev, Bice Chini, Thierry Durroux, Bernard Mouillac, Maithe Corbani and Gilles Guillon.  Oxytocin and Vasopressin Agonists and Antagonists as Research Tools and Potential Therapeutics.  J. Neuroendocrinology 24:609-628, 2012.

Marta Busnelli, Elisabetta Bulgheroni, Maurice Manning, Gunnar Kleinau and Bice Chini.  Selective and Potent Agonists and Antagonists for Investigating the Role of Mouse Oxytocin Receptors.  Journal of Pharmacology and Experimental Therapeutics.  Fast Forward published on May 30, 2013 as D01:10.1124/jpet.113.202994.