Tuning the Hydrolytic Stability of Next Generation
Maleimide Cross-Linkers Enables Access to Albumin-Antibody Fragment
Conjugates and tri-scFvs
Version 2 2018-02-20, 19:19
Version 1 2018-01-31, 13:54
Posted on 2018-02-20 - 19:19
We
describe investigations to expand the scope of next generation
maleimide cross-linkers for the construction of homogeneous protein–protein
conjugates. Diiodomaleimides are shown to offer the ideal properties
of rapid bioconjugation with reduced hydrolysis, allowing the cross-linking
of even sterically hindered systems. The optimized linkers are exploited
to link human serum albumin to antibody fragments (Fab or scFv) as
a prospective half-life extension platform, with retention of antigen
binding and robust serum stability. Finally, a triprotein conjugate
is formed, by linking scFv antibody fragments targeting carcinoembryonic
antigen. This tri-scFv is shown to infer a combination of greater
antigen avidity and increased in vivo half-life,
representing a promising platform for antibody therapeutic development.
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Forte, Nafsika; Livanos, Maria; Miranda, Enrique; Morais, Maurício; Yang, Xiaoping; Rajkumar, Vineeth S.; et al. (2018). Tuning the Hydrolytic Stability of Next Generation
Maleimide Cross-Linkers Enables Access to Albumin-Antibody Fragment
Conjugates and tri-scFvs. ACS Publications. Collection. https://doi.org/10.1021/acs.bioconjchem.7b00795
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AUTHORS (9)
NF
Nafsika Forte
ML
Maria Livanos
EM
Enrique Miranda
MM
Maurício Morais
XY
Xiaoping Yang
VR
Vineeth S. Rajkumar
KC
Kerry A. Chester
VC
Vijay Chudasama
JB
James R. Baker
KEYWORDS
scFv antibody fragmentsantigen bindingNext Generation Maleimide Cross-Linkers Enables Accessgeneration maleimide cross-linkershalf-life extension platformantibody fragmentsantigen aviditytri-scFvvivo half-lifeserum stabilityoptimized linkerstriprotein conjugateHydrolytic Stabilitycarcinoembryonic antigenAlbumin-Antibody Fragment Conjugatesserum albumin