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Featured researches published by Kent E. Göklen.


Biotechnology Progress | 2009

Virus filtration of high‐concentration monoclonal antibody solutions

Bruno F. Marques; David J. Roush; Kent E. Göklen

The ability to process high‐concentration monoclonal antibody solutions (> 10 g/L) through small‐pore membranes typically used for virus removal can improve current antibody purification processes by eliminating the need for feed stream dilution, and by reducing filter area, cycle‐time, and costs. In this work, we present the screening of virus filters of varying configurations and materials of construction using MAb solutions with a concentration range of 4–20 g/L. For our MAbs of interest—two different humanized IgG1s—flux decay was not observed up to a filter loading of 200 L/m2 with a regenerated cellulose hollow fiber virus removal filter. In contrast, PVDF and PES flat sheet disc membranes were plugged by solutions of these same MAbs with concentrations >4 g/L well before 50 L/m2. These results were obtained with purified feed streams containing <2% aggregates, as measured by size exclusion chromatography, where the majority of the aggregate likely was composed of dimers. Differences in filtration flux performance between the two MAbs under similar operating conditions indicate the sensitivity of the system to small differences in protein structure, presumably due to the impact of these differences on nonspecific interactions between the protein and the membrane; these differences cannot be anticipated based on protein pI alone. Virus clearance data with two model viruses (XMuLV and MMV) confirm the ability of hollow fiber membranes with 19 ± 2 nm pore size to achieve at least 3–4 LRV, independent of MAb concentration, over the range examined.


Journal of Chromatography A | 1998

Preparative high-performance liquid chromatography of echinocandins

David J. Roush; Firoz D. Antia; Kent E. Göklen

Abstract The isolation of fermentation derived small bioactive molecules remains extremely challenging due to the presence of many analogues with similar physicochemical behavior. Removal of analogue impurities typically involves crystallization and/or preparative HPLC. The normal-phase preparative HPLC for the purification of fermentation derived echinocandins is described. Resolution of key impurities from the product of interest, pneumocandin B o , is accomplished using a ternary ethyl acetate–methanol–water mobile phase with silica gel as the sorbent. Plate counts, measured with small molecules, show that the column efficiency is excellent under the operating conditions despite the use of an irregular silica and unusually high levels (greater than 6%) of water in the mobile phase. The results of optimization studies indicate the product solubility, retention and resolution of key analogue impurities are strong functions of the ternary mobile phase composition. The normal-phase HPLC process was optimized by carrying out eluent flow-rate (linear velocity) and column loading studies. The results of these experimental studies indicate that both yield and productivity are a function of linear velocity and product loading and that a tradeoff exists between these two parameters.


Bioorganic & Medicinal Chemistry Letters | 1995

Isolation, structure determination and squalene synthase activity of L-731,120 and L-731,128, alkyl citrate analogs of zaragozic acids A and B

Guy H. Harris; Claude Dufresne; Henry Joshua; Leslie Koch; Deborah L. Zink; Peter Salmon; Kent E. Göklen; Marc M. Kurtz; Deborah J. Rew; James D. Bergstrom; Kenneth E. Wilson

Abstract Two new alkyl citrates, L-731,120 and L-731,128, with alkyl chains corresponding to those of zaragozic acids A and B, were isolated as minor components of large scale fungal fermentations producing zaragozic acid A and B. They are submicromolar inhibitors of squalene synthase in vitro .


Biotechnology Progress | 2006

Normal Phase High‐Performance Liquid Chromatography of Pneumocandins: In Situ Modification of Silica with l‐Proline To Separate Structural Analogues

Joseph Nti-Gyabaah; Firoz D. Antia; Mary Ellen Dahlgren; Kent E. Göklen

Lipopeptides such as pneumocandin B0 are often produced by fermentation processes. Many compounds with similar structures (structural analogues), and hence similar physiochemical properties, are coproduced in the fermentation. We employed high performance liquid chromatography using silica gel as the stationary phase and a ternary ethyl acetate/MeOH/water mobile phase to separate pneumocandin B0 from these structural analogues. Despite extensive efforts to optimize this system, two key structural analogues, pneumocandin E0 and pneumocandin B5, continued to be poorly resolved from the main product peak (pneumocandin B0). As a result, feed load was restricted and productivity was limited. In situ modification of the silica gel stationary phase with l‐proline or other amino acids significantly enhances the resolution of the two key structural analogues from the compound of interest, enabling a two‐fold increase in productivity. Results of a systematic study showed that the amine group in l‐proline and other amino acids plays a key role in the modification of the surface of the silica gel to mediate the selectivity enhancement.


Biotechnology and Bioengineering | 2008

Maximizing productivity of chromatography steps for purification of monoclonal antibodies.

Nihal Tugcu; David J. Roush; Kent E. Göklen


The Journal of Antibiotics | 1998

Inhibition of Fungal Sphingolipid Biosynthesis by Rustmicin, Galbonolide B and Their New 21-Hydroxy Analogs

Guy H. Harris; Ali Shafiee; M. Angeles Cabello; James E. Curotto; Olga Genilloud; Kent E. Göklen; Myra B. Kurtz; Mark Rosenbach; Peter Salmon; Rosemary A. Thornton; Deborah L. Zink; Suzanne M. Mandala


Industrial & Engineering Chemistry Research | 2005

Using CFD To Understand How Flow Patterns Affect Retention of Cell-Sized Particles in a Tubular Bowl Centrifuge

Mayur Jain; Madhavaram Paranandi; David J. Roush; Kent E. Göklen; William J. Kelly


Archive | 2004

Stationary phases and a purification process using the stationary phases

Firoz D. Antia; Russell Boyd; Jimmy O. DaSilva; Kent E. Göklen; Joseph Nti-Gyabaah; Christopher J. Welch


Journal of Chemical Technology & Biotechnology | 1995

Development of a pilot‐scale microfiltration harvest for the isolation of physostigmine from Streptomyces griseofuscus broth

Gregory Russotti; Kent E. Göklen; James Wilson


Archive | 2003

Using amines or amino acids as mobile phase modifiers in chromatography

Kent E. Göklen; Joseph Nti-Gyabaah; Firorz D. Antia; Mary Ellen Dahlgren

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