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Case Western Reserve team discovers 'smart' insulin molecule
Date:4/12/2010

linical trials.

"The goal of all drug therapies is to make therapeutic molecules more selective, in other words, more effective with less complications. We've sought to accomplish this with our engineering a new and "smarter" insulin molecule, as the hormone's primary job is to bind to the key receptors that regulate blood glucose concentration (designated the insulin receptor), not cancer-related receptors," says Dr. Weiss.

The new insulin analog exhibits reduced binding to a receptor that can drive cell growth, called the IGF receptor. Protein engineering spans both basic science and its translation to clinical care. Critical to reaching the translational goal of improved insulin therapy was an interdisciplinary team, including endocrinologist, Dr. Ismail-Beigi; biochemist, Nelson Phillips, PhD, associate professor of biochemistry; X-ray crystallographer, Zhu-li Wan, PhD, instructor in biochemistry; and receptor expert, Jonathan Whittaker, PhD, associate professor of biochemistry.

The study concludes and demonstrates, "The potential of interfacial zinc-binding sites, introduced by design, to modify the pharmacokinetics of a protein in a subcutaneous depot. Such bottom-up control of assembly illustrates general principles of supramolecular chemistry and their application to nanobiotechnology.

"Zinc stapling of insulin exemplifies a general strategy to modify the pharmacokinetic and biological properties of a subcutaneous protein depot. The engineering of novel lattice contacts in protein crystals can thus enable control of supramolecular assembly as a therapeutic protein nanotechnology."


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Contact: Christina DeAngelis
christina.deangelis@case.edu
216-368-3635
Case Western Reserve University
Source:Eurekalert

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