Human serum albumin (HSA) plays a pivotal role in drug release from its delivery vehicles such as cyclodextrins (CDs) by binding to the drugs. Here molecular recognition and binding of a drug mimic (CD1) to HSA have been explored in a microfluidic channel when CD1 is encapsulated in β-cyclodextrin (βCD) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TRIMEB), respectively, to investigate whether change of the host vehicle modulate the rate of drug binding to the serum protein. Molecular recognition of βCD encapsulated CD1 by HSA occurs by the conformational selection fit mechanism leading to rapid binding of CD1 to HSA (k1 ~ 700 s-11) when the βCD/CD1 complex interacts with HSA. In contrary, HSA recognizes CD1 encapsulated in TRIMEB by an induced fit mechanism leading to a significantly slower binding rate (k1 ~ 20.8 s-1) of the drug mimic to the protein. Thus molecular recognition controls the rate of HSA binding by CD1 which in turn modulates the rate of delivery of the drug mimic from its macrocyclic hosts. The remarkable change in the molecular recognition pathway of CD1 by HSA, upon change of the host from βCD to TRIMEB, originates from significantly different conformational flexibility of the host/drug mimic complexes.
Keywords: Conformational flexibility; Microfluidic channel; Molecular recognition.
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