Crystal structures of the HCl salts of pseudopeptidic macrocycles display “knobs into holes” hydrophobic interactions between aliphatic side chains [PDF]
The crystal structures of three HCl salts of pseudopeptidic macrocycles show a H-bonding tubular stack of the rings, where the amino acidic side chains (Val, Leu, Ile) display an inter-columnar “knobs into holes” hydrophobic interaction ...
Ignacio Alfonso +2 more
exaly +6 more sources
Production of bispecific antibodies in "knobs-into-holes" using a cell-free expression system. [PDF]
Bispecific antibodies have emerged in recent years as a promising field of research for therapies in oncology, inflammable diseases, and infectious diseases. Their capability of dual target recognition allows for novel therapeutic hypothesis to be tested, where traditional mono-specific antibodies would lack the needed mode of target engagement.
Xu Y +10 more
europepmc +5 more sources
Heavy and light chain pairing of bivalent quadroma and knobs-into-holes antibodies analyzed by UHR-ESI-QTOF mass spectrometry. [PDF]
The quadroma antibody represents the first attempt to produce a bispecific heterodimeric IgG antibody by somatic fusion of 2 hybridoma cells each expressing monoclonal antibodies with distinctive specificities. However, because of random heavy and light chain pairing, the desired functional bispecific antibody represents only a small fraction of the ...
Schaefer W +6 more
europepmc +5 more sources
Knobs-into-holes antibody production in mammalian cell lines reveals that asymmetric afucosylation is sufficient for full antibody-dependent cellular cytotoxicity. [PDF]
Knobs-into-holes is a well-validated heterodimerization technology for the third constant domain of an antibody. This technology has been used to produce a monovalent IgG for clinical development (onartuzumab) and multiple bispecific antibodies. The most advanced uses of this approach, however, have been limited to E.
Shatz W +8 more
europepmc +5 more sources
Effect of allotypic variation of human IgG1 on the thermal stability of disulfide-linked knobs-into-holes mutants of the Fc for stable bispecific antibody design. [PDF]
AbstractBackgroundDisulfide-linked knobs-into-holes (dKiH) mutation is a well-validated antibody engineering technique to force heterodimer formation of different Fcs for efficient production of bispecific antibodies. An artificial disulfide bond is created between mutated cysteine residues in CH3 domain of human IgG1 Fc whose positions are 354 of the “
Akiba H, Satoh R, Nagata S, Tsumoto K.
europepmc +5 more sources
Crystal structure of an anti-Ang2 CrossFab demonstrates complete structural and functional integrity of the variable domain. [PDF]
Bispecific antibodies are considered as a promising class of future biotherapeutic molecules. They comprise binding specificities for two different antigens, which may provide additive or synergistic modes of action.
Sebastian Fenn +12 more
doaj +6 more sources
Nonclinical immunogenicity risk assessment for knobs-into-holes bispecific IgG1 antibodies
Bispecific antibodies, including bispecific IgG, are emerging as an important new class of antibody therapeutics. As a result, we, as well as others, have developed engineering strategies designed to facilitate the efficient production of bispecific IgG ...
Wen-Ting K. Tsai +15 more
doaj +3 more sources
Construction of bispecific antibodies by specific pairing between the heavy chain and the light chain using removable SpyCatcher/SnoopCatcher units [PDF]
During the production of bispecific antibodies (bsAbs), nonspecific pairing results in low yields of target bsAb molecules, an issue known as the “mispairing problem.” Several antibody engineering techniques have been developed to overcome mispairing ...
Jyunna Yoshida +7 more
doaj +2 more sources
Physicochemical and biological characterization of a bispecific antibody in a CrossMab/KIH format that targets EGFR and VEGF-A [PDF]
IntroductionBispecific antibodies (BsAbs) are a class of antibody therapeutics engineered in various molecular formats to bind two distinct antigens and potentially mediate multiple biological effects.
Safiat Ayinde +3 more
doaj +2 more sources
Rapid affinity-based purification of multi-specific antibodies using Kappa Select and Protein L [PDF]
Multispecific antibodies (msAbs) are becoming more prevalent as formats of choice for therapeutic antibody development due to their ability to modulate multiple biological targets.
Kalie Mix +6 more
doaj +2 more sources

