RESUMEN
A variety of Fc domain engineering approaches for abrogating the effector functions of mAbs exists. To address some of the limitations of the current Fc domain silencing approaches, we are exploring a less commonly considered option which relies on the deletion of the hinge. Removal of the hinge domain in humanized IgG1 and IgG4 mAbs obliterates their ability to bind to activating human Fc gamma receptors I and IIIA, while leaving their ability to engage their target antigen intact. Deletion of the hinge also reduces binding to the Fc neonatal receptor, although Fc engineering allows partial recovery of affinity. Engineering of the CH3 domain, stabilizes hinge deleted IgG4s and prevents Fab arm exchange. The faster clearing properties together with the pacified Fc make modality of the hinge deleted mAb an appealing solution for therapeutic and diagnostic applications.
RESUMEN
Hydrothermal chemistry has been exploited in the preparation of a series of manganese(II), iron(II), and nickel(II) triazolate frameworks, [Mn7(trz)8(CH3CO2)4(OH)2].2.5H2O (1.2.5H2O), [Mn5(Htrz)2(SO4)4(OH)2] (2), [Fe5(Htrz)2(SO4)4(OH)2] (3), [Fe3(Htrz)3(HSO4)(SO4)2(OH)].H2O (4.H2O), [Ni3(trz)3(OH)3(H2O)4].5H2O (5.5H2O), and [Ni3(trz)5(OH)].2.5H2O (6.2.5H2O). The materials all exhibit three-dimensional structures, reflecting the tendency of triazole/triazolate ligands to bridge multiple metal sites. A prominent characteristic of the structures is the presence of embedded metal clusters as building blocks: heptanuclear MnII units in 1, pentanuclear MII sites in 2 and 3, and trinuclear MII clusters in 4 and 5. The presence of the pentanuclear and trinuclear clusters of magnetic metal cations in 2-5 is reflected in the unusual magnetic characteristics of these materials, all of which exhibit spin frustration. The compound 5.5H2O reversibly desorbs/sorbs solvent. However, the dehydrated phase does not adsorb methanol, N2, O2, or H2, presumably as a consequence of the highly polar void volume and the narrow channels connecting the larger cavities of the void structure.