Effects of polymer molecular weight on the size, activity, and stability of PEG-functionalized trypsin.
Polymer conjugation increases an enzyme's circulation time and stability for use as a therapeutic agent, but this attachment indubitably affects its properties. Covalent attachment of multiple polyethylene glycol chains with sizes of either 2, 5, 10, or 20 kDa increases the molecular weight and hydrodynamic radius of the model enzyme trypsin. The sizes of these polymer-enzyme conjugates are increased to be within the recommended limits for PDEPT applications. The T(d) increases from 49 to 60 °C to expand the enzyme's workable range of conditions. This functionalization with PEG polymers of varying lengths maintains trypsin's enzymatic activity. Conjugate activities are 79-120% that of native trypsin at room temperature and 221-432% that of trypsin at 37 °C.
Department of Chemistry, 47 Lab Campus Drive, Williams College, Williamstown, Massachusetts 01267, United States.
Karen
K
Chiu
Lauren L
LL
Agoubi
Iris
I
Lee
Matthew T
MT
Limpar
James W
JW
Lowe
Sarah L
SL
Goh
D004795:Enzyme Stability / Q000187:drug effects; D008970:Molecular Weight; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D011108:Polymers; D014357:Trypsin / Q000737:chemistry / Q000378:metabolism*
D011108:Polymers; D011092:Polyethylene Glycols; D014357:Trypsin