RESUMO
There are many proteins that can multi-task. Transferrin, widely known as an iron-binding protein, is one such example of a multi-tasking protein. In this review, the multiple biological actions of transferrin, including its growth and cytoprotective activities, are discussed with the view of highlighting the potential therapeutic applications of this protein.
Assuntos
Transferrina/química , Transferrina/fisiologia , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/uso terapêutico , Transporte Biológico , Transplante de Medula Óssea , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Ferro/metabolismo , Neoplasias/tratamento farmacológico , Radioterapia , Receptores da Transferrina/fisiologia , Transferrina/uso terapêuticoRESUMO
Vitamin D-binding protein (DBP) is a multi-functional plasma protein with many important functions. These include transport of vitamin D metabolites, control of bone development, binding of fatty acids, sequestration of actin and a range of less-defined roles in modulating immune and inflammatory responses. Exploitation of the unique properties of DBP could enable the development of important therapeutic agents for the treatment of a variety of diseases.
Assuntos
Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Osteopetrose/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Proteína de Ligação a Vitamina D/metabolismo , Proteína de Ligação a Vitamina D/uso terapêutico , Actinas/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Fatores Imunológicos/uso terapêutico , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Macrófagos/metabolismo , Ligação Proteica , Proteína de Ligação a Vitamina D/química , Proteína de Ligação a Vitamina D/imunologiaRESUMO
This study evaluated the feasibility of substituting expanded bed adsorption (EBA) chromatography for an existing chromatographic purification process for the isolation of prothrombin complex concentrate (PCC) from Cohn Supernatant I. The EBA chromatography (Streamline) resins were compared to the current DEAE-cellulose resin for the extraction of PCC from Cohn SNI. EBA chromatography resins efficiently bound PCC from Cohn SNI at a significantly higher flow rate of up to 300 cm/h compared to 30 cm/h for the current DEAE-cellulose process. Composition and yield of the recovered PCC reflected the elution conditions used. The results indicate that EBA chromatography could be used to efficiently produce PCC comparable to existing products.
Assuntos
Fatores de Coagulação Sanguínea/isolamento & purificação , Proteínas Sanguíneas/química , Cromatografia/métodos , Resinas de Troca Aniônica/farmacologia , Técnicas de Laboratório Clínico , Indústria Farmacêutica/métodos , Humanos , Protrombina/isolamento & purificação , Soroalbumina Bovina/químicaRESUMO
A common problem in the manufacture of liquid protein therapeutics is the tendency for aggregation and particle formation on extended storage. One aspect of processing that might contribute to particle formation is pumping. In the present study, we demonstrate that lobe pumps can promote aggregation in albumin preparations. This is accentuated where the clearance between the pump housing and lobes is increased. Under these conditions, the pump efficiency decreases, resulting in increased exposure of the protein to the pump environment. Depending on the inherent physicochemical stability of the protein, this can lead to aggregate formation, which can influence the long-term stability characteristics of the product.
Assuntos
Albuminas/química , Biotecnologia/métodos , Albuminas/isolamento & purificação , Humanos , Imunoglobulina G/químicaRESUMO
Using SPH (smoothed particle hydrodynamics), the motion of a lobe pump under load was simulated in order to predict the level of shear stress experienced by a protein solution. By varying the gap size between the lobes and pump housing, variations in pump efficiency and shear stress were determined. The simulations indicated that pump shear was dependent on gap size, with shear stress levels (0-40 Pa) correlating with those estimated in previous albumin-pumping studies. As gap size increased, the number of fluid particles experiencing low shear (<10 Pa) increased, whereas those experiencing high shear (>20 Pa) showed a decreasing trend. The pump efficiency, however, decreased with gap size, requiring more lobe revolutions to pass a unit volume. Taken together, these observations indicate that lobe pumps operated with increased gaps between the rotors and the housing result in larger number of particles within the fluid experiencing shear stresses. Moreover, the simulations indicate that it is best to use larger lobe pumps operated at high efficiency to transfer protein-containing solutions.
Assuntos
Albuminas/química , Biotecnologia/métodos , Albuminas/isolamento & purificação , Algoritmos , Fenômenos Biomecânicos , Simulação por Computador , Humanos , Modelos TeóricosRESUMO
The present paper describes an anion-exchange chromatography method to separate iron-free apo-Tf (apo-transferrin) from albumin and IgG in Cohn supernatant I. The method uses DEAE-fast flow Sepharose chromatography along with optimized protein concentration (5%, w/v) and column operation conditions (40 g/l, conductivity <1.0 mS/cm) to resolve apo-Tf from IgG and albumin. The single step purifies apo-Tf to >90% and provides an efficient means to obtain commercial quantities of the protein.
Assuntos
Cromatografia por Troca Iônica , Transferrina/isolamento & purificação , Fracionamento Químico , Cromatografia DEAE-Celulose , Eletroforese em Gel de Poliacrilamida , Estudos de Viabilidade , Humanos , Imunoglobulina G/isolamento & purificação , Albumina Sérica/isolamento & purificaçãoRESUMO
A common problem in the manufacture of liquid protein therapeutics is the tendency for aggregation and particle formation on extended storage. Analytical techniques are required to study the propensity of solutions to form aggregates and particles and to allow the investigation of the effect of conditions encountered during manufacture and storage. A key challenge is to utilize appropriate specific and sensitive techniques to allow the early detection of initial aggregation events, thereby avoiding the need to resort to extended stability trials. The present review evaluates a range of techniques for the detection of changes in protein conformation and the formation of aggregates and particles. It is hoped that the availability of this information will encourage and facilitate studies to resolve stability issues associated with protein therapeutics.