Classification of Peptides According to their Blood-Brain Barrier Influx

Abstract

An increasing number of studies demonstrate the ability of peptides to cross the blood-brain barrier (BBB), opening perspectives for a new class of therapeutics for central nervous system diseases. However, information on the BBB transport of peptides suffer from a wide variety in used methods and experimental set-up. Therefore, it is currently difficult, if not impossible, to classify peptides according to their BBB influx characteristics. To allow direct comparison of BBB influx results of peptides, we introduce a classification method and unified response for BBB influx transport of peptides. First, the results of BBB influx response types (i.e. Kin (MTR), Kin (Perfusion), Pin vitro and Pin vivo), which quantitatively express brain influx, were classified into five classes of BBB influx magnitude based on the distribution of these results for the individual response types. Then, these classes were converted to a BBBin-response, representing a scaled value ranging from zero (no influx) to ten (high influx), independent from the BBB influx response type from which it was derived. This unified response can immediately be applied for new BBB influx results of peptides and represents a ballpark figure for BBB influx and allows direct comparison and ranking of peptides independent of the response type.

Biodistribution of the cyclotide MCoTI‐II, a cyclic disulfide‐rich peptide drug scaffold

“…The brain influx rate (K in ) and the distribution volume (V i ) obtained from fitting the model is shown in Table 1. As expected, the negative control, BSA, showed lower K in and V i values than the positive control, dermorphin, even though it is generally regarded to have relatively low influx [38]. For MCoTI-II, a K in value of 9.37 × 10 À5 μl/g/min was obtained, which is lower than that of BSA, indicating that it has no or very limited influx into the brain.…”

Blood-brain barrier transport kinetics of the cyclic depsipeptide mycotoxins beauvericin and enniatins

“…For the first model using The BBB-influx classification system for peptides as proposed by Stalmans et al (2015b) indicated that BEA and ENNs are located in class 5, corresponding to a very high brain influx, which was also confirmed by comparing our obtained influx data of BEA/ENNs with those of other peptides (Van Dorpe et al, 2012).…”

“…As negative and positive control, 125 I labelled BSA and dermorphin were used, respectively, to assure the overall validity of the experiment (Stalmans et al, 2015b). Furthermore, the influence of the ethanol-containing dose formulations on the BBB integrity was also investigated in a radioactive MTR influx study with 125 I radiolabelled BSA.…”

“…where Cbrain(T) is the concentration of cyclic depsipeptide mycotoxin in the brain at time T (ng/g), Cs(T) is the concentration of peptide in serum at time T (ng/µL), K is the net clearance (μL/(g×min)), K1 is the unidirectional clearance (μL/(g×min)), Vg is the brain tissue distribution volume (µL/g), and V0 is the vascular brain distribution volume, experimentally determined as the brain distribution volume of radioiodinated BSA (14.8 µL/g) (Stalmans et al, 2015b). Consequently, the ratio of Cbrain(T) and Cs(T) leads to the unit 'µL serum/g brain',…”

Topics and trends in artificial intelligence assisted human brain research

“…For EEG Signals Analysis, Li et al [62] proposed an innovative hybrid automated sleep stage scoring method called HyCLASSS with the basis of single channel EEG. For Molecule, to enable comparing blood-brain barrierinflux (BBB) results of peptides directly, Stalmans et al [63] proposed an innovative classification approach and unified response for BBB transport of peptides. For Brain-Computer-Interface, Schettini et al [64] proposed and evaluated a novel approach for the automated recalibration of the classifier's parameters.…”