Designed hydrophilic and charge mutations of the fibronectin domain: towards tailored protein biodistribution.

ABSTRACT: Engineered proteins are attractive affinity scaffolds for molecular imaging and drug delivery. Although exquisite binding specificity and affinity can be engineered, many proteins exhibit off-target uptake, particularly in the kidneys and liver, from physiologic effects. We quantified the ability to alter renal and hepatic uptake via hydrophilic and charge mutations. As a model protein, we used the 10th type III domain of human fibronectin, which has been engineered to bind many targets and has been validated for molecular imaging. We screened rational mutants, identified by structural and phylogenetic analyses, to yield eight mutations that collectively substantially increase protein hydrophilicity. Mutation of two parental clones yielded four domains with a range of hydrophilicity. These

SUBMITTER: Hackel BJ 

PROVIDER: S-EPMC3449399 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature