权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

An amphipathic reagent to extract stabilize and purify proteins

用于提取稳定和纯化蛋白质的两亲试剂

基本信息

批准号：
BB/G010412/1
负责人：
Timothy Dafforn
金额：
$ 52.84万
依托单位：
University of Birmingham
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2009
资助国家：
英国
起止时间：
2009 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FG010412%2F1
关键词：
amphipathic reagent extract stabilize purify

项目摘要

The development of new therapeutic agents has undergone a revolution during the last two decades. For 80 years medicines have almost exclusively consisted of relatively small chemicals. However, biotherapeutics agents have recently emerged as the fastest growing type of new drugs being developed. They include antibodies that are part of our body's immune systems that fight off infections. Antibodies are a type of molecule called a protein; these proteins are highly complex and very fragile in contrast to the chemicals that were used in medicines in the past. Most biotherapeutic agents in clinical use are drugs manufactured in microorganisms or substances that are produced by living organisms. They include antibodies and enzymes. Most biotech pharmaceuticals are recombinant proteins produced by genetic engineering. Specific examples include cytokines like insulin and interferons, recombinant enzymes that combat cystic fibrosis (dornase alfa) and heart disease (Alteplase), hormones (Erythropoietin and human growth hormone), clotting factors, vaccines and monoclonal antibodies. Biotech pharmaceuticals have major limitations. Many are difficult to purify intact, and are unstable with limited shelf lives. Also, some are not absorbable in a medically useful form through the gastrointestinal tract, lungs or skin. Impurity is also a common problem, as they most be purified from complex biological sources. Protein impurities can cause allergic reactions or alter therapeutic effects. Hence, production of a stable protein particle that can easily be purified is very important. We have developed a new solution that increases both the yield and stability of the biotherapeutic. The chemical (called SPS) that provides this solution can act in two ways that helps the production of certain biotherapeutcics. Firstly it can be used to help release the product from the microorganisms in which it has been made. Once released the SPS can act like a stabilising bracelet, wrapping around proteins that are not generally stable in water preventing them from loosing activity. Both of these abilities will greatly increase the efficiency of biotherapeutic production which should result in cheaper and more available drugs. As an added advantage the reagent is safe for use in human beings and has been shown to facilitate the uptake of drugs into the body, increasing their effectiveness. This again has the potential to reduce drug costs. This project aims to demonstrate the effectiveness of SPS in biotherapeutic development while at the same time develop protocols so that it can be easily adopted by companies making biotherapeutics.

在过去的二十年中，新治疗剂的开发经历了一场革命。80年来，药物几乎完全由相对较小的化学物质组成。然而，生物治疗剂最近已成为发展最快的新药类型。它们包括抗体，抗体是我们身体免疫系统的一部分，可以抵抗感染。抗体是一种称为蛋白质的分子;这些蛋白质非常复杂，与过去用于药物的化学物质相比非常脆弱。临床使用的大多数生物治疗剂是微生物制造的药物或活生物体产生的物质。它们包括抗体和酶。大多数生物技术药物是通过基因工程生产的重组蛋白质。具体实例包括细胞因子如胰岛素和干扰素、对抗囊性纤维化（阿法链霉菌素酶）和心脏病（阿替普酶）的重组酶、激素（促红细胞生成素和人生长激素）、凝血因子、疫苗和单克隆抗体。生物技术制药有很大的局限性。许多难以完整纯化，并且不稳定，保质期有限。此外，一些不能以医学上有用的形式通过胃肠道、肺或皮肤吸收。杂质也是一个常见的问题，因为它们大多数是从复杂的生物来源中纯化的。蛋白质杂质会引起过敏反应或改变治疗效果。因此，生产可容易纯化的稳定蛋白质颗粒是非常重要的。我们已经开发出一种新的解决方案，既提高了产量，又提高了生物柴油的稳定性。提供这种解决方案的化学物质（称为SPS）可以通过两种方式发挥作用，帮助生产某些生物治疗药物。首先，它可以用来帮助产品从微生物中释放出来。一旦被释放，SPS可以像一个稳定的手镯一样，包裹在通常在水中不稳定的蛋白质周围，防止它们失去活性。这两种能力将大大提高生物制药的生产效率，从而产生更便宜和更容易获得的药物。作为一个额外的优势，该试剂可安全用于人类，并已被证明有助于药物进入体内，提高其有效性。这也有可能降低药品成本。该项目旨在证明SPS在生物治疗开发中的有效性，同时开发协议，以便生物治疗公司可以轻松采用。