Krishna Kumar

Krishna Kumar

Robinson Professor of Chemistry
Member, Cancer Center, Tufts Medical Center
Tufts University
Medford, MA


Molecular Design of Peptide Therapeutics for Global Diseases

Obesity, Type 2 Diabetes, T2D, and related metabolic disorders afflict hundreds of millions worldwide. State of the art treatments include analogues of the endogenous gut peptide hormones called "incretins." The two principal peptides that form this class, Glucagon-like Peptide 1, GLP-1, and Glucose-dependent Insulinotropic Peptide, GIP, stimulate their cognate receptors, GLP-1R and GIPR, in different tissues with the primary function of maintaining glucose homeostasis in addition to having neuro- and cardioprotective effects. These peptides however suffer from poor metabolic stability and are rapidly degraded by the ubiquitous serine protease, dipeptidyl peptidase IV, DPP-4.


We describe here the design and development of potent peptide analogues that are completely refractory to hydrolytic enzyme action while retaining full biological activity, potency, and efficacy. As general modulators of the gut-brain axis, these peptide hormones have also high promise for untreated neurological indications such as Alzheimer's and Parkinson's diseases, and traumatic brain injury, TBI. Furthermore, the platform allows for the design of hundreds of derivatives with the ability to tune the onset and duration of action, potency, efficacy, and providing a method for modulating gut and blood brain barrier, BBB, penetration.

This lecture will describe the fundamental design principles, molecular pharmacology and in vivo data. Some of the compounds described here rival or better the compounds used in the clinic today and could serve as a model platform for discovery of clinically relevant molecular entities.


Kathleen Sicinski 1, Vittorio Montanari 1, Krishna Kumar 1,2,3


1 Department of Chemistry, Tufts University, Medford, MA 02155
2 Department of Biomedical Engineering, Tufts University, Medford, MA 02155
3 Cancer Center, Tufts Medical Center, Boston, MA 02110

Lecture Images

Krishna Kumar presenting at APS2019 Krishna Kumar presenting at APS2019 Krishna Kumar presenting at APS2019