High Throughput Combinatorial Formatting of PcrV Nanobodies for Efficient Potency Improvement.

ABSTRACT: Improving potencies through concomitant blockage of multiple epitopes and avid binding by fusing multiple (different) monovalent Nanobody building blocks via linker sequences into one multivalent polypeptide chain is an elegant alternative to affinity maturation. We explored a large and random formatting library of bivalent (combinations of two identical) and biparatopic (combinations of two different) Nanobodies for functional blockade of Pseudomonas aeruginosa PcrV. PcrV is an essential part of the P. aeruginosa type III secretion system (T3SS), and its oligomeric nature allows for multiple complex binding and blocking options. The library screening yielded a large number of promising biparatopic lead candidates, revealing significant (and non-trivial) preferences in terms of Nanobody bu

SUBMITTER: De Tavernier E 

PROVIDER: S-EPMC4946937 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature