Glucagon, New and Improved!

Glucagon Improvements via Pyridyl-Ala Substitutions

Glucagon is a critical peptide hormone that plays a critical physiological role in mobilization of hepatic glucose through stimulation of gluconeogenesis and glycogenolysis. For insulin dependent diabetics, who frequently encounter hypoglycemia, glucagon may be used as a subcutaneous injection in emergency situations to counter a bout with severe hypoglycemia. Certain properties of glucagon cause this peptide to be unusually unstable with a tendency to degrade rapidly and to form insoluble fibrils. Administration usually involves reconstitution in a sterile acidified diluent immediately prior to injection. Recently in the lab of Richard DiMarchi, glucagon analogs with substation of 3-and 4-pyridyl Ala 3-Pal and 4-Pal) in place of the aromatic amino acids Phe and Tyr were synthesized which had dramatic improvements to its biophysical properties while maintaining high potency relative to native glucagon. The glucagon analog with substitution of 3-Pal at positions 6,10 and 13 with an Aib16  demonstrated far superior properties in vivo in models of insulin-dependent hypoglycemia in pigs and rats (DOI: 10.1021/acs.jmedchem.6b00840).

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Dr. Michael W. Pennington

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Dr. Michael Pennington joined Peptides International in December 2010 as Chief Technology Officer. On January 1, 2013, Dr. Pennington's role became that of President and Chief Executive Officer. After doctoral research at University of Florida, he joined the pharmaceutical industry in the Department of Biotechnology at Schering-Plough. He joined Bachem Biosciences in King of Prussia, PA as a Principle Scientist in the Peptide Chemistry department. Dr. Pennington served as the Group Director for Bachem Biosciences before being appointed as President and C.O.O., a positioned he maintained from 2000 – 2010. He built and directed an internationally recognized peptide chemistry team focused on producing complex peptides and toxins. Dr. Pennington was a member of Bachem Forschungausschuss, the International Research and Development from 2000 – 2010. He has extensive collaborations with both industrial and academic scientists and maintains an extramurally funded research program on several peptide toxins. He is a founder of Airmid Inc., a biotech venture company dedicated to advancing two of his discoveries into clinical development for autoimmune diseases. Dr. Pennington has been awarded four patents and over 85 peer reviewed scientific articles, and serves as an editor of International Journal of Peptide Research and Therapeutics and Current Peptide and Protein Letters. He holds a Bachelor of Chemistry degree from the University of North Carolina at Chapel Hill and a Ph.D. from University of Florida at Gainesville.