Oligomeric particle reagents and methods of use thereof

A method for producing an oligomeric particle reagent comprising streptavidin or a streptavidin mutein, the method comprising:

• incubating a plurality of activated streptavidin or streptavidin mutein molecules comprising a thiol-reactive functional group capable of reacting with a thiol functional group and a plurality of thiolated streptavidin or streptavidin mutein molecules comprising one or more thiol functional group, thereby generating a particle composition comprising the oligomeric particles comprising streptavidin or a streptavidin mutein;
• separating the oligomeric particles from monomer and/or smaller oligomeric molecules;
• and
• contacting the oligomeric particle with a stabilization agent, wherein the stabilization agent reduces an amount of N-substituted iminothiolane present on lysine residues of the oligomeric particle reagents, thereby producing the oligomeric particle reagent.

A method for producing oligomeric particle reagents, the method comprising:

• (a) incubating a first plurality of streptavidin or streptavidin mutein molecules with an activation agent under conditions to convert one or more amines to a thiol-reactive group capable of reacting with a thiol functional group, thereby generating a plurality of activated streptavidin or streptavidin mutein molecules;
• (b) incubating a second plurality of streptavidin or streptavidin mutein molecules with a thiolating agent that adds or is capable of adding a thiol functional group to one or more lysine residue, thereby generating a plurality of thiolated streptavidin or streptavidin mutein molecules;
• and
• (c) incubating the plurality of activated streptavidin or streptavidin mutein molecules with the plurality of thiolated streptavidin or streptavidin mutein molecules, thereby generating a particle composition comprising the oligomeric particle reagents;
• wherein the method is carried out under conditions in which, at the time of initiation of the incubation in (c), the plurality of thiolated streptavidin or streptavidin mutein molecules are such that at least 60% of the lysines, on average, comprise a thiol functional group, and/or at least 10 lysines, on average, per thiolated streptavidin or streptavidin mutein tetramer comprise a thiol functional group.