Protein Engineering for Therapeutics, Part A

369 Pages·2012·11.25 MB·English

by  K. Dane Wittrup and Gregory L. Verdine (Eds.)

METHODS IN ENZYMOLOGY
Editors-in-Chief
JOHN N. ABELSON MELVIN I. SIMON
AND
Division of Biology
California Institute of Technology
Pasadena, California
Founding Editors
SIDNEY P. COLOWICK NATHAN O. KAPLAN
AND
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C
ONTRIBUTORS
GiuliaAgnello
Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas,
USA
JagadishBeloor
Department of Bioengineering and Institute for Bioengineering and Biopharma-
ceuticalResearch,HanyangUniversity,Seoul,SouthKorea
MichaelT.Bethune
DivisionofBiology,CaliforniaInstituteofTechnology,Pasadena,California,USA
Yu(Joshua)Cao
ImmunopharmacologyandTargetedTherapyLaboratory,DepartmentofExperi-
mentalTherapeutics,M.D.AndersonCancerCenter,Houston,Texas,USA
JasonR.Cantor
DepartmentofChemicalEngineering,UniversityofTexas,Austin,Texas,USA
AshutoshChilkoti
Department of Biomedical Engineering and Center for Biologically Inspired
MaterialsandMaterialSystems,DukeUniversity,Durham,NorthCarolina,USA
DarylC.Drummond
MerrimackPharmaceuticals,Cambridge,Massachusetts,USA
ChelcieH.Eller
Department of Biochemistry, University of Wisconsin–Madison, Madison,
Wisconsin,USA
TarekM.Fahmy
DepartmentofBiomedicalEngineering,YaleUniversity,NewHaven,Connecticut,
USA
GeorgeGeorgiou
Department of Chemical Engineering; Institute for Cellular and Molecular
Biology; Section of Molecular Genetics and Microbiology; and Department of
BiomedicalEngineering,UniversityofTexas,Austin,Texas,USA
TariqGhayur
BiologicsDepartment,AbbottBioresearchCenter,Worcester,Massachusetts,USA
ix
x Contributors
JijieGu
BiologicsDepartment,AbbottBioresearchCenter,Worcester,Massachusetts,USA
BrianD.Harms
MerrimackPharmaceuticals,Cambridge,Massachusetts,USA
WafaHassouneh
Department of Biomedical Engineering, Duke University, Durham, North
Carolina,USA
MarkE.Hayes
MerrimackPharmaceuticals,Cambridge,Massachusetts,USA
ZhaohuaHuang
MerrimackPharmaceuticals,Cambridge,Massachusetts,USA
JeffreyD.Kearns
MerrimackPharmaceuticals,Cambridge,Massachusetts,USA
ChaitanKhosla
DepartmentofChemicalEngineering;DepartmentofChemistry,andDepartment
ofBiochemistry(bycourtesy),StanfordUniversity,Stanford,California,USA
DmitriB.Kirpotin
MerrimackPharmaceuticals,Cambridge,Massachusetts,USA
NeerajKohli
MerrimackPharmaceuticals,Cambridge,Massachusetts,USA
TadKornaga
MerrimackPharmaceuticals,Cambridge,Massachusetts,USA
PritiKumar
Department of Internal Medicine/Section for Infectious Diseases, Yale School of
Medicine,NewHaven,Connecticut,USA
Sang-KyungLee
Department of Bioengineering and Institute for Bioengineering and Biopharma-
ceuticalResearch,HanyangUniversity,Seoul,SouthKorea;DepartmentofInter-
nal Medicine/Section for Infectious Diseases, Yale School of Medicine, New
Haven,Connecticut,USA
JoE.Lomax
Graduate Program in Cellular & Molecular Biology, University of Wisconsin–
Madison,Madison,Wisconsin,USA
RobertP.Lyon
SeattleGenetics,Bothell,Washington,USA
Contributors xi
Mi-AeLyu
ImmunopharmacologyandTargetedTherapyLaboratory,DepartmentofExperi-
mentalTherapeutics,M.D.AndersonCancerCenter,Houston,Texas,USA
SarahR.MacEwan
Department of Biomedical Engineering, Duke University, Durham, North
Carolina,USA
JamesD.Marks
Department of Anesthesia and Perioperative Care, University of California, San
Francisco,California,USA
DavidL.Meyer
SeattleGenetics,Bothell,Washington,USA
KhalidA.Mohamedali
ImmunopharmacologyandTargetedTherapyLaboratory,DepartmentofExperi-
mentalTherapeutics,M.D.AndersonCancerCenter,Houston,Texas,USA
UlrikB.Nielsen
MerrimackPharmaceuticals,Cambridge,Massachusetts,USA
CharlesO.Noble
MerrimackPharmaceuticals,Cambridge,Massachusetts,USA
VasilikiPanayiotou
DepartmentofChemicalEngineering,UniversityofTexas,Austin,Texas,USA
RonaldT.Raines
Department of Biochemistry and Department of Chemistry, University of
Wisconsin–Madison,Madison,Wisconsin,USA
SaravananRajan
TerrenceDonnellyCentreforCellularandBiomolecularResearch,Universityof
Toronto,Toronto,Ontario,Canada
MichaelG.Rosenblum
ImmunopharmacologyandTargetedTherapyLaboratory,DepartmentofExperi-
mentalTherapeutics,M.D.AndersonCancerCenter,Houston,Texas,USA
BirgitSchoeberl
MerrimackPharmaceuticals,Cambridge,Massachusetts,USA
PeterD.Senter
SeattleGenetics,Bothell,Washington,USA
JocelynR.Setter
SeattleGenetics,Bothell,Washington,USA
xii Contributors
SachdevS.Sidhu
Terrence Donnelly Centre for Cellular and Biomolecular Research; Banting and
Best Department of Medical Research; and Department of Molecular Genetics,
UniversityofToronto,Toronto,Ontario,Canada
AlyssaSiefert
DepartmentofBiomedicalEngineering,YaleUniversity,NewHaven,Connecticut,
USA
EverettM.Stone
DepartmentofBiomedicalEngineering,UniversityofTexas,Austin,Texas,USA
StephenV.Su
MerrimackPharmaceuticals,Cambridge,Massachusetts,USA
YuZhou
Department of Anesthesia and Perioperative Care, University of California, San
Francisco,California,USA
P
REFACE
ThesetwovolumesofMethodsinEnzymologycoverengineeringapproaches
to the development of protein biopharmaceuticals, which represent a
significantandrapidlygrowingproportionofdrugsales.Particularadvan-
tages of proteins as drugs relative to small organic molecules include high
affinity and specificity afforded by a larger molecular recognition surface
and much lower probability of off-target toxicities due to metabolic
byproducts. The primary disadvantage to date has been the pharmacoki-
netic inaccessibility of intracellular drug targets to proteins and peptides,
although vigorous efforts at overcoming this limitation are beginning to
bear fruit.
The protein biopharmaceutical field was born with the advent of
recombinant DNA expression systems for natural human protein agonists
such as insulin, human growth hormone, erythropoietin, and granulocyte
colony-stimulating factor. Humanization of mouse antibodies opened the
playing field to novel molecules that specifically bound to and blocked
receptors and ligands important in a variety of diseases. In vitro directed
evolutiontechnologieshaveenabledfurtherexplorationofnonnativestruc-
tures and topologies for target antagonism or delivery of therapeutic pay-
loads. It should be pointed out that to date protein engineering has made
minimal progress in engineering the agonists which were the first protein
biopharmaceuticals. Such engineered agonists could enable more subtle
redirection of innate homeostatic regulatory pathways than the relatively
crude tools of antibody antagonism or parenteral oversupply of naturally
occurring protein and peptide agonists.
We provide here only an overview representing the wide spectrum of
approachesinthisfield.Thefirstsectioncoverssomeaspectsofantibodies,
byfarthedominantclassofproteinbiopharmaceuticalsatthepresenttime.
Thesecondsectionprovidesexampleswhereproteintargetingisexploited
to deliver a payload conjugated to the proteins. In the third section of the
firstvolume,examples ofengineeredtherapeuticenzymes areprovided.In
the first section of the second volume, peptides are considered, enabling
chemicalsynthesisandmorefacileintracellulardelivery,giventheirsmaller
size. The second section describes a number of leading efforts to engineer
molecularrecognitionontoascaffoldotherthanthatofanantibody.Inthe
third and final section, pharmacokinetics of protein drugs is discussed with
xiii
xiv Preface
respect to delivery to tumors, intracellular targets, and across the blood–
brain barrier.
We particularly thank the authors of these contributions for their thor-
ough and clear exposition of the state of the art in their respective
specializations.
K. DANE WITTRUP AND GREGORY L. VERDINE
M E
ETHODS IN NZYMOLOGY
VOLUMEI.PreparationandAssayofEnzymes
EditedbySIDNEYP.COLOWICKANDNATHANO.KAPLAN
VOLUMEII.PreparationandAssayofEnzymes
EditedbySIDNEYP.COLOWICKANDNATHANO.KAPLAN
VOLUMEIII.PreparationandAssayofSubstrates
EditedbySIDNEYP.COLOWICKANDNATHANO.KAPLAN
VOLUMEIV.SpecialTechniquesfortheEnzymologist
EditedbySIDNEYP.COLOWICKANDNATHANO.KAPLAN
VOLUMEV.PreparationandAssayofEnzymes
EditedbySIDNEYP.COLOWICKANDNATHANO.KAPLAN
VOLUMEVI.PreparationandAssayofEnzymes(Continued)
PreparationandAssayofSubstrates
SpecialTechniques
EditedbySIDNEYP.COLOWICKANDNATHANO.KAPLAN
VOLUMEVII.CumulativeSubjectIndex
EditedbySIDNEYP.COLOWICKANDNATHANO.KAPLAN
VOLUMEVIII.ComplexCarbohydrates
EditedbyELIZABETHF.NEUFELDANDVICTORGINSBURG
VOLUMEIX.CarbohydrateMetabolism
EditedbyWILLISA.WOOD
VOLUMEX.OxidationandPhosphorylation
EditedbyRONALDW.ESTABROOKANDMAYNARDE.PULLMAN
VOLUMEXI.EnzymeStructure
EditedbyC.H.W.HIRS
VOLUMEXII.NucleicAcids(PartsAandB)
EditedbyLAWRENCEGROSSMANANDKIVIEMOLDAVE
VOLUMEXIII.CitricAcidCycle
EditedbyJ.M.LOWENSTEIN
VOLUMEXIV.Lipids
EditedbyJ.M.LOWENSTEIN
VOLUMEXV.SteroidsandTerpenoids
EditedbyRAYMONDB.CLAYTON
xv
xvi MethodsinEnzymology
VOLUMEXVI.FastReactions
EditedbyKENNETHKUSTIN
VOLUMEXVII.MetabolismofAminoAcidsandAmines(PartsAandB)
EditedbyHERBERTTABORANDCELIAWHITETABOR
VOLUMEXVIII.VitaminsandCoenzymes(PartsA,B,andC)
EditedbyDONALDB.MCCORMICKANDLEMUELD.WRIGHT
VOLUMEXIX.ProteolyticEnzymes
EditedbyGERTRUDEE.PERLMANNANDLASZLOLORAND
VOLUMEXX.NucleicAcidsandProteinSynthesis(PartC)
EditedbyKIVIEMOLDAVEANDLAWRENCEGROSSMAN
VOLUMEXXI.NucleicAcids(PartD)
EditedbyLAWRENCEGROSSMANANDKIVIEMOLDAVE
VOLUMEXXII.EnzymePurificationandRelatedTechniques
EditedbyWILLIAMB.JAKOBY
VOLUMEXXIII.Photosynthesis(PartA)
EditedbyANTHONYSANPIETRO
VOLUMEXXIV.PhotosynthesisandNitrogenFixation(PartB)
EditedbyANTHONYSANPIETRO
VOLUMEXXV.EnzymeStructure(PartB)
EditedbyC.H.W.HIRSANDSERGEN.TIMASHEFF
VOLUMEXXVI.EnzymeStructure(PartC)
EditedbyC.H.W.HIRSANDSERGEN.TIMASHEFF
VOLUMEXXVII.EnzymeStructure(PartD)
EditedbyC.H.W.HIRSANDSERGEN.TIMASHEFF
VOLUMEXXVIII.ComplexCarbohydrates(PartB)
EditedbyVICTORGINSBURG
VOLUMEXXIX.NucleicAcidsandProteinSynthesis(PartE)
EditedbyLAWRENCEGROSSMANANDKIVIEMOLDAVE
VOLUMEXXX.NucleicAcidsandProteinSynthesis(PartF)
EditedbyKIVIEMOLDAVEANDLAWRENCEGROSSMAN
VOLUMEXXXI.Biomembranes(PartA)
EditedbySIDNEYFLEISCHERANDLESTERPACKER
VOLUMEXXXII.Biomembranes(PartB)
EditedbySIDNEYFLEISCHERANDLESTERPACKER
VOLUMEXXXIII.CumulativeSubjectIndexVolumesI-XXX
EditedbyMARTHAG.DENNISANDEDWARDA.DENNIS
VOLUMEXXXIV.AffinityTechniques(EnzymePurification:PartB)
EditedbyWILLIAMB.JAKOBYANDMEIRWILCHEK