Fast Acting Insulins from Fish-Hunting Cone Snail Venom

Insulins in the venom of certain fish-hunting cone snails facilitate prey capture by rapidly inducing hypoglycemic shock. One such insulin, Conus geographus G1 (Con-Ins G1), is the smallest known insulin found in nature and lacks the C-terminal segment of the B chain that, in human insulin (hIns), mediates engagement of the insulin receptor and assembly of the hormone’s hexameric storage form. Removal of this segment (residues B23–B30) in human insulin results in substantial loss (< 0.1%) of receptor affinity. Menting, et al. (http://www.nature.com/nsmb/journal/v23/n10/full/nsmb.3292.html) found that Con-Ins G1 is monomeric, strongly binds the human insulin receptor and activates receptor signaling. Con-Ins G1 thus is a naturally occurring B-chain-minimized mimetic of human insulin. The crystal structure of Con-Ins G1 reveals a tertiary structure highly similar to that of human insulin.  These findings are intriguing in that they indicate that Con-Ins G1 contains a structural element that mitigates the lack of an equivalent to the critical hIns residue PheB24. The crystal structure of Con-Ins G1 coupled with molecular modeling suggests that this element is formed by the tyrosine residues at position B15 and possibly also B20, whose side chains then act as surrogates for the key receptor-engaging residue PheB24 in hIns. These structural findings provide a platform for the design of a novel class of therapeutic human insulin analogs that are intrinsically monomeric and rapid acting and indicates how Con-Ins G1’s lack of an equivalent to the key receptor-engaging residue PheB24 is mitigated. Their findings  on Con-Ins-G1 may facilitate efforts to design ultrarapid-acting therapeutic insulins.

Industry News , Biologically Active Peptides

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.