Advertisement

If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.

ENJOY UNLIMITED ACCES TO C&EN

Materials

Chemists Design Insulin That’s Responsive To Blood Glucose Levels

Phenylboronic acid groups on the designer compound bind glucose, switch on insulin

by Celia Henry Arnaud
February 16, 2015 | A version of this story appeared in Volume 93, Issue 7

[+]Enlarge
A designer insulin contains a glucose-binding phenylboronic acid (red) and an albumin-binding alkyl chain (blue) linked to a lysine residue (black).
Structure of a designer insulin that contains a glucose-binding phenylboronic acid and an albumin-binding alky chain linked to a lysine residue.
A designer insulin contains a glucose-binding phenylboronic acid (red) and an albumin-binding alkyl chain (blue) linked to a lysine residue (black).

For people with type 1 diabetes, insulin injections can keep blood glucose levels down. To make the injection process easier for patients, chemists have been tweaking insulin’s composition. One long-lasting insulin formulation, for example, contains a hydrophobic alkyl chain that increases circulation half-life by binding to albumin and other proteins. The activity of that long-lasting insulin, however, is independent of the amount of glucose in the blood, so changes in blood sugar are not always regulated quickly enough. Daniel G. Anderson, Robert S. Langer, and coworkers at MIT set out to make long-lasting insulin that is also glucose-responsive (Proc. Natl. Acad. Sci. USA 2015, DOI: 10.1073/pnas.1424684112). They did this by adding phenylboronic acid, which binds glucose, to the end of the alkyl chain. The team tested four variants, each with a different modification to the phenylboronic acid group, on a mouse model of type 1 diabetes. The researchers administered glucose tolerance tests four hours, seven hours, and 10 hours after injecting one of the variants or native insulin. Only two of the variants continued working after 10 hours. The best one contained a fluoro-modified phenylboronic acid and worked better than the clinically available long-lasting insulin.

Article:

This article has been sent to the following recipient:

0 /1 FREE ARTICLES LEFT THIS MONTH Remaining
Chemistry matters. Join us to get the news you need.