Laboratory of Biomedical Chemistry, Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy PAS, Wrocław, Poland.
Laboratory of Biology of Stem and Neoplastic Cells, Hirszfeld Institute of Immunology and Experimental Therapy PAS, Wrocław, Poland.
Ann N Y Acad Sci. 2019 Dec;1457(1):128-141. doi: 10.1111/nyas.14201. Epub 2019 Aug 12.
Metallacarboranes are anionic boron clusters with high affinity to serum albumin, ability to cross biological membranes, and no apparent toxicity in vitro and in vivo. Thus, conjugation with cobalt bis(1,2-dicarbollide), [COSAN] , ([3,3'-Co(1,2-C B H ) ] ) may improve the properties of therapeutic peptides or proteins at both molecular and systemic levels. Here, we conjugated [COSAN] with the therapeutic peptide thymosin β4 (Tβ4), which has a pleiotropic activity that results in enhanced healing and regeneration of injured tissues. Using fluorescence quenching of human serum albumin and surface plasmon resonance techniques, we showed that the conjugates have a high affinity to human serum albumin. Using an in vitro wound closure assay, we showed that conjugation with [COSAN] enhances the activity of Tβ4 toward fibroblasts (MSU1.1 cell line). These results indicate an application of metallacarboranes in the development of analogs of various therapeutic peptides/proteins with superior pharmacological properties.
金属卡宾硼烷是带负电荷的硼簇，对血清白蛋白具有高亲和力、能够穿过生物膜、在体外和体内均无明显毒性。因此，与二聚(1,2-二碳硼烷)钴络合物([COSAN]，([3,3'-Co(1,2-CB 11 H 11 ) ] ))缀合可能会在分子和系统水平上改善治疗性肽或蛋白质的性质。在这里，我们将治疗性肽胸腺素 β4(Tβ4)与[COSAN]缀合，Tβ4 具有多种活性，可增强受损组织的愈合和再生。通过人血清白蛋白的荧光猝灭和表面等离子体共振技术，我们表明缀合物与人血清白蛋白具有高亲和力。通过体外伤口闭合测定，我们表明与[COSAN]缀合可增强 Tβ4 对成纤维细胞(MSU1.1 细胞系)的活性。这些结果表明金属卡宾硼烷可应用于开发具有优越药理学性质的各种治疗性肽/蛋白质类似物。
