Structural Characterization of PEGylated Protein Therapeutics ...


"Structural Characterization of PEGylated Protein Therapeutics
using Gas-Phase Ion/Molecule Chemistry and Ion Mobility Tandem Mass Spectrometry"

               Paul Schnier

               Department of Molecular Structure

               Amgen, Thousand Oaks, CA "


Conjugation of polyethylene glycol (PEG) to a protein therapeutic can safely improve pharmacokinetic properties, thus PEG and its derivatives have found wide application in the biopharmaceutical industry.  PEGs used in these applications are typically polydisperse and generally of high molecular weight, obfuscating direct analytical characterization.  Here, we demonstrate the use of ion mobility in the separation of  PEGs of different chain length, facilitating direct measurement of MW and polydispersity of pegylated peptides/proteins.  Ion-molecule proton-transfer chemistry, in either the ion mobility cell or source, can be used to enable charge stripping of the PEG ions in order to further simplify the spectrum.  Tandem mass spectrometry of the mobility separated ions allows the site of PEGylation to be unambiguously determined. Additionally, a novel functional analysis algorithm to quantitatively compare the 3D topology of ion mobility MS spectra has been developed.  This approach allows for the direct quantitation of low level impurities and degradation products present in these samples; this methodology can be used in a high throughput fashion to fingerprint heterogeneous PEGylated therapeutics.   For these applications, ion mobility coupled with mass spectrometry offers several analytical advantages over mass spectrometry alone, including enhanced dynamic range, increased sensitivity and specificity.

Speaker Background

Paul Schnier received his Ph.D. in Physical Chemistry from the University of California, Berkeley, in 1998, followed a by post-doctoral fellowship at the Oak Ridge National Laboratory.  He has worked in the biopharmaceutical industry for the last eight years, and is currently Principal Scientist in the Department of Molecular Structure at Amgen.  His current research interests are focused on the application of novel mass spectrometric, NMR, and biophysical methodologies to drug discovery.



DATE:           Tuesday, Nov. 13
Location:       Michael's Restaurant at Shoreline Park, Mountain View

                                     See directions below.

Timing:   6:00  PM  social hour
             7:00 PM   dinner
             8:00  PM  presentations begin

Cost:             $30 with advance registration
                Half price for students, retired, and unemployed. (late fee still applies, if applicable)
                Free if you attend just the lectures at 8:00 PM.
                           (but please let us know for headcount)
           $40 after registration deadline, if possible -- please contact us to inquire.

Deadline for registration:    5 PM Friday, Nov. 9 (but please try to do so earlier if you can; it helps)

DIRECTIONS to Michael's at Shoreline Park:
Restaurant's web page directions
From 101 in Mountain View, take the Shoreline Boulevard
Exit toward the Bay. Drive past the Shoreline Amphitheater
and go straight ahead on Shoreline, entering into Shoreline Park.  
After a mile or so inside the park, a sign for Michael's will
direct you to turn left into the parking lot for Michael's Restaurant.

Address:   2960 N Shoreline Blvd.
Restaurant phone:   650-962-1014
Do NOT call restaurant for reservations.

PLEASE NOTE:  we accept cash or checks, but are unable to accept payment by credit card at this time.   You may pay at the door.

Please register on the web page

Or, contact:
            David Robinson

Dinner Selections:
            Chicken Florentine
            Grilled Vegetable Brochette

You should receive confirmation of your registration; if not, please contact us again.

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