Search Results - igor+kaltashov

                                            

The incidence of brain and central nervous system (CNS) infections is rising at an alarming rate, while treatment options remain very limited. Only about 5% of existing small-molecule medicines can cross the blood-brain barrier (BBB), and none of the currently approved protein therapeutics are capable of doing so. With increasing resistance of pathogens to common antibiotics and dire side effects of the immune system’s inflammatory response (frequently leading to brain abscess), CNS infections present doctors with a grave challenge. Clearly, there exists a significant and unmet need for novel biopharmaceuticals that can control CNS and brain infections in the most efficient way without eliciting an immune response from the patient. Dr. Kaltashov’s team has developed novel protein conjugates composed of covalently linked transferrin (a promising drug carrier than can cross the BBB) and lysozyme (an antibacterial enzyme that is not normally present in cerebrospinal fluid). These conjugates are designed to penetrate the BBB and combat Gram-positive bacterial infections of the brain and CNS while eliminating the risks and complications associated with conventional pharmaceutical treatments.

Applications:

Targeted protein therapy, designed to cross the blood-brain barrier, can potentially treat Gram-positive bacterial infections of the brain and central nervous system (e.g., meningitis, encephalitis, brain abscess) that result from complications due to skull fractures, medical implants, untreated infections, or immune system compromise.

This technology provides a temperature-controlled electrospray ionization (ESI) source that allows for highly precise and accurate characterization of the thermal stability and aggregation of proteins by ESI mass spectrometry (MS). The ESI source was designed to eliminate artifacts that interfere with the detection of temperature-induced changes of biopolymer properties. It minimizes biopolymer degradation prior to the analysis, and incorporates a long heat shield to greatly improve thermal control during sample introduction into the ESI interface. This technology, coupled with high specificity of MS detection, enables the study of both reversible and irreversible processes of biopolymers in solution, and allows the early stages of heat-induced protein aggregation to be characterized in detail by monitoring both conformational changes and formation of oligomeric complexes as a function of temperature.