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COMPOSITIONS BASED ON STABILIZED FIBRONECTIN DOMAINS, METHODS AND AREAS OF THEIR APPLICATION

机译:基于稳定的纤连蛋白域的组合物,其应用方法和领域

摘要

1. A polypeptide containing a framework-based molecule containing loop domains topologically similar to type III fibronectin domains, where the polypeptide has an amino acid sequence based on a consensus sequence of type III fibronectin domains having the amino acid sequence of SEQ ID NO: 16, in which the specific residues of the SEQ sequence ID NO: 16 replaced, which increases the chemical stability and thermal stability of the specified molecule based on the framework. 2. The polypeptide according to claim 1, wherein the thermal stability is measured as the melting temperature (Tm) using differential scanning calorimetry, and the chemical stability is measured as [D] by the stability to the chloride induced guanidine denaturation. The polypeptide according to claim 2, in which the Tm is increased compared to a molecule based on the frame having the amino acid sequence of SEQ ID NO: 16 with an energy value of from about 4.18 kJ (1 kcal) to about 50.21 kJ (12 kcal). four. The polypeptide according to claim 2, in which [D] compared with the frame-based molecule having the amino acid sequence of SEQ ID NO: 16, increases from about 0.1 to about 2.0 M, and free energy (AG) compared to a skeleton-based molecule having the amino acid sequence of SEQ ID NO: 16 increases from 0.418 to about 41.8 kJ / mol (from 0.1 to about 10 kcal / mol) .5. A polypeptide containing a framework-based molecule containing loop domains topologically similar to type III fibronectin domains, where the polypeptide has an amino acid sequence based on a consensus sequence of type III fibronectin domains having an amino acid
机译:1.一种多肽,其包含基于框架的分子,所述分子包含拓扑类似于III型纤连蛋白结构域的环结构域,其中所述多肽具有基于具有氨基酸序列SEQ ID NO:16的III型纤连蛋白结构域的共有序列的氨基酸序列。 ,其中SEQ ID NO:16的特定残基被替换,这增加了基于框架的特定分子的化学稳定性和热稳定性。 2.根据权利要求1的多肽,其中使用差示扫描量热法将热稳定性测量为解链温度(Tm),并通过对氯化物诱导的胍变性的稳定性将化学稳定性测量为[D]。 3.根据权利要求2所述的多肽,其中,与基于具有SEQ ID NO:16的氨基酸序列的框的分子相比,Tm增加,所述框的能量值为约4.18kJ(1kcal)至约50.21kJ( 12大卡)。四。 3.根据权利要求2所述的多肽,其中,[D]与具有SEQ ID NO:16的氨基酸序列的基于框架的分子相比,从约0.1M增加至约2.0M,并且与骨架相比具有自由能(AG)具有SEQ ID NO:16的氨基酸序列的α-基分子从0.418增加到约41.8kJ / mol(从0.1到约10kcal / mol).5。一种包含基于框架的分子的多肽,该分子包含与拓扑结构类似于III型纤连蛋白结构域的环状结构域,其中该多肽具有基于具有氨基酸的III型纤连蛋白结构域的共有序列的氨基酸序列

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