ABSTRACT
The combination of potent chemical moieties with biologically active proteins is key to some of today's most innovative therapeutic drugs. In order to obviate any chemical modification of the proteins, we present a novel and powerful strategy for the selective conjugation of recombinant protein domains with synthetically derived peptides via a cucurbit[8]uril host-guest chemistry approach.
Subject(s)
Peptides/chemistry , Recombinant Proteins/chemistryABSTRACT
Iatrogenic preterm prelabor rupture of membranes (iPPROM) remains the main complication after invasive interventions into the intrauterine cavity. Here, the proteolytic stability of mussel-mimetic tissue adhesive (mussel glue) and its sealing behavior on punctured fetal membranes are evaluated. The proteolytic degradation of mussel glue and fibrin glue were compared in vitro. Critical pressures of punctured and sealed fetal membranes were determined under close to physiological conditions using a custom-made inflation device. An inverse finite element procedure was applied to estimate mechanical parameters of mussel glue. Mussel glue was insensitive whereas fibrin glue was sensitive towards proteolytic degradation. Mussel glue sealed 3.7mm fetal membrane defect up to 60mbar (45mmHg) when applied under wet conditions, whereas fibrin glue needed dry membrane surfaces for reliable sealing. The mussel glue can be represented by a neo-Hookean material model with elastic coefficient C(1)=9.63kPa. Ex-vivo-tested mussel glue sealed fetal membranes and resisted pressures achieved during uterine contractions. Together with good stability in proteolytic environments, this makes mussel glue a promising sealing material for future applications.
