Improving the solubility of single domain antibodies using VH-like hallmark residues.

ABSTRACT: Single domain antibodies (sdAbs) can be generated from variable regions of heavy-chain antibodies, which lack light chain and CH1 region. They have attracted attention due to their small size and molecular characteristics. Hydrophilic hallmark amino acids at framework region 2 (FR2) are key residues involved in the solubility of sdAbs. Nevertheless, previous studies reported that several sdAbs with human VH-like hydrophobic hallmark residues were soluble in a monomeric state and suggested that solubility also depends on the amino acid sequences in the complementarity-determining region. In this study, we obtained two sdAbs (sdAb A and B) with VH-like hallmark residues and low solubility from an alpaca immune library. We introduced VHH-like mutations (V37Y, G44E, L45R, W47L) into the hallma

SUBMITTER: Uto Y 

PROVIDER: S-EPMC12168134 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature