The present invention provides a single domain antibody (sdAb) scaffold comprising one or more than one non canonical disulfide bond in the framework region (FR). The one or more than one non canonical disulfide bond may be formed between cysteines introduced by mutations in FR2 and FR3. In the case where the sdAb scaffold is a VH the Cys may be introduced at any one of positions (47 49) and any one of positions (67 71) based on Kabat numbering in one example the Cys may be introduced at positions (49) and (69) based on Kabat numbering. In the case where the sdAb scaffold is a VL the Cys residues may be introduced at any one of positions 46 49 and any one of positions (62 66) based on Kabat numbering in one example the Cys residues may be introduced at positions (48 and 64) based on Kabat numbering.
