John Engen, asso­ciate pro­fessor of chem­istry and chem­ical biology, is at the fore­front of research that will advance drug dis­covery and devel­op­ment by making it easier to ana­lyze cer­tain kinds of pro­teins, their role in dis­ease, and their inter­ac­tions with drugs and each other.

Pro­tein drugs, called bio­phar­ma­ceu­ti­cals, rep­re­sent the fastest growing seg­ment of the phar­ma­ceu­tical industry, Engen noted. His cur­rent research at North­eastern University’s Bar­nett Insti­tute of Chem­ical and Bio­log­ical Analysis has recently been fea­tured in Chem­ical and Engi­neering News and the journal Nature.

Drug devel­op­ment is highly depen­dent on the study of pro­teins, par­tic­u­larly cell-​​membrane pro­teins, which account for 20 to 30 per­cent of all pro­teins in humans and rep­re­sent nearly two-​​thirds of the pro­teins that can be tar­geted by drugs. How­ever, these pro­teins are dif­fi­cult to study because they are asso­ci­ated with lipids (mol­e­cules that make up the cell mem­brane). Most bio­an­a­lyt­ical tech­niques are not com­pat­ible with the com­bi­na­tion of lipids and pro­teins, espe­cially those that are used to reveal the three-​​dimensional struc­ture of proteins.

Engen’s recent work uses tiny slices of lipid, called nan­odiscs, to develop a method to probe the struc­ture of mem­brane proteins.

Mem­brane pro­teins can be inserted into the nan­odiscs, which look like little Fris­bees, in a way that mimics how they are found in cells,” said Engen. “Since the nan­odiscs are much more com­pat­ible with many existing bio­an­a­lyt­ical methods, it is then pos­sible to study the shape of the pro­teins that are in the discs.”

Engen’s research, in col­lab­o­ra­tion with Waters Cor­po­ra­tion of Mil­ford, Mass., has led to the devel­op­ment of a new instru­mental system for the analysis of pro­teins using Ultra­p­er­for­mance Liquid Chro­matog­raphy (UPLC).

UPLC, including a spe­cial­ized ver­sion that reveals the three-​​dimensional shape of pro­teins, rep­re­sents the future of sep­a­ra­tion sci­ence, said Engen. “We can study impor­tant things like how pro­teins par­tic­i­pate in dis­ease, how drugs interact with pro­teins, pro­tein com­plexes, and how pro­tein drugs behave during manufacturing.”

Recently Engen, in col­lab­o­ra­tion with researchers at Har­vard Med­ical School and the Dana-​​Farber Cancer Insti­tute, used the spe­cial­ized UPLC system to help under­stand the inhi­bi­tion mech­a­nism of a new type of anti-​​leukemia drug.