Development of a generic strategy for the stabilisation of peptide-based therapeutics

开发稳定肽疗法的通用策略

• 批准号: nhmrc : 456073
• 负责人: Dr Richard Clark
• 金额: $ 29.55万
• 依托单位: The University of Queensland
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/development-generic-strategy-based-therapeutics/76827
• 关键词: Development; generic; strategy; stabilisation; peptide

There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. However, there are still a number of hurdles that need to be overcome before this source of promising pharmaceuticals can fulfil their vast potential. One of the biggest challenges in the development of peptides and proteins as drugs is overcoming their poor stability in the human body. The broad aim of this research proposal is to develop a novel strategy that provides therapeutically promising peptides and proteins the ability to resist the body s natural degradation pathways so they are able to reach their biological target. To develop this strategy we will use the recently discovered peptide hepcidin as a model system. Hepcidin is the major iron-regulatory hormone in the human body and incorrect levels of this hormone result in either iron overload (haemochromatosis), when there is not enough hepcidin produced by the body, or anemia of inflammation when there is too much hepcidin. The development of hepcidin-based therapeutic agents to treat these conditions has the potential to have significant impact as it has been estimated that up to 1 in 300 Australians are affected by haemochromatosis during their lifetimes. Unfortunately, unmodified peptides, like hepcidin, are of limited therapeutic value due to their poor stability within the human body. This research proposal describes the development of stabilised hepcidin analogues with the potential of being useful drug leads for the treatment of haemochromatosis.

人们对开发用于治疗多种疾病的生物活性肽和蛋白质有着巨大的兴趣。然而，在这种有前途的药物来源能够发挥其巨大潜力之前，仍然需要克服许多障碍。开发肽和蛋白质作为药物的最大挑战之一是克服它们在人体内的稳定性差。这项研究提案的主要目的是开发一种新的策略，为有治疗前景的肽和蛋白质提供抵抗人体自然降解途径的能力，使它们能够达到其生物学目标。为了开发这种策略，我们将使用最近发现的肽hepcidin作为模型系统。铁调素是人体中主要的铁调节激素，这种激素的不正确水平会导致铁过载（血色素沉着症），当身体产生的铁调素不足时，或者当铁调素过多时会导致炎症性贫血。开发基于铁调素的治疗药物来治疗这些疾病有可能产生重大影响，因为据估计，每300名澳大利亚人中就有1人在其一生中受到血色病的影响。不幸的是，未修饰的肽，如铁调素，由于其在人体内的稳定性差，具有有限的治疗价值。这项研究计划描述了稳定的铁调素类似物的开发，其具有成为治疗血色病的有用药物先导的潜力。