PMID- 24274767 OWN - NLM STAT- MEDLINE DCOM- 20150415 LR - 20151119 IS - 1520-5827 (Electronic) IS - 0743-7463 (Linking) VI - 29 IP - 50 DP - 2013 Dec 17 TI - Low temperature thermal dependent Filgrastim adsorption behavior detected with ToF-SIMS. PG - 15573-8 LID - 10.1021/la403607m [doi] AB - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) detected changes in Filgrastim (granulocyte colony stimulating growth factor, G-CSF) adsorption behavior at a solid interface when exposed to temperatures as low as 35 degrees C, i.e., before thermal denaturation, was detected by circular dichroism (CD) or dynamic light scattering (DLS). Biopharmaceuticals rely on maintaining sufficient conformation to impart correct biological function in vivo. Stability of such molecules is critical during synthesis, storage, transport, and administration. CD analysis indicated loss of structure at temperatures greater than ~60 degrees C, while DLS detected aggregation at ~42 degrees C. Furthermore, we demonstrate the nature of G-CSF interaction with a surface was altered rapidly and at relatively low temperatures. Specifically, after 10 min thermal treatment, changes in adsorption behavior occurred at 35 degrees C indicated by principal component analysis of spectra as primarily due to increasing yields of methionine fragments. This was likely to be due to either altering the preferential protein orientation upon adsorption or greater denaturation exposing the hydrophobic core. This investigation demonstrates the sensitivity of ToF-SIMS in studying biopharmaceutical adsorption and conformational change and can assist with studies into promoting their stability. FAU - Kempson, Ivan M AU - Kempson IM AD - Ian Wark Research Institute, University of South Australia , Mawson Lakes, S.A. 5095, Australia. FAU - Chang, Patrick AU - Chang P FAU - Bremmell, Kristen AU - Bremmell K FAU - Prestidge, Clive A AU - Prestidge CA LA - eng PT - Journal Article DEP - 20131204 PL - United States TA - Langmuir JT - Langmuir : the ACS journal of surfaces and colloids JID - 9882736 RN - 0 (Recombinant Proteins) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - PVI5M0M1GW (Filgrastim) SB - IM MH - Adsorption MH - Circular Dichroism MH - Filgrastim MH - Granulocyte Colony-Stimulating Factor/*chemistry MH - Recombinant Proteins/chemistry MH - Spectrometry, Mass, Secondary Ion MH - Surface Properties MH - Temperature EDAT- 2013/11/28 06:00 MHDA- 2015/04/16 06:00 CRDT- 2013/11/27 06:00 PHST- 2013/11/27 06:00 [entrez] PHST- 2013/11/28 06:00 [pubmed] PHST- 2015/04/16 06:00 [medline] AID - 10.1021/la403607m [doi] PST - ppublish SO - Langmuir. 2013 Dec 17;29(50):15573-8. doi: 10.1021/la403607m. Epub 2013 Dec 4.