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In Situ Imaging of Pathological Collagen by Electrostatic Repulsion-Destabilized Peptide Probes
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-09-08 , DOI: 10.1021/acsabm.0c00710 Xiangdong Cai 1 , Wenyu Wei 1 , Zhao Liu 2 , Zhongtian Bai 2 , Junqiang Lei 2 , Jianxi Xiao 1
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-09-08 , DOI: 10.1021/acsabm.0c00710 Xiangdong Cai 1 , Wenyu Wei 1 , Zhao Liu 2 , Zhongtian Bai 2 , Junqiang Lei 2 , Jianxi Xiao 1
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The development of robust collagen assays is crucial in the diagnosis and treatment of various pathological conditions. Peptide probes composed of the (Gly-Pro-Hyp)n sequences have received extensive attention for their remarkable collagen-targeting capability, which unfortunately has been severely impaired by their high triple helical stability. Herein, we report an efficient strategy to reduce the triple helical propensity of the (Gly-Pro-Hyp)n sequences by electrostatic repulsion. A series of peptides consisting of the (Gly-Pro-Hyp)7 sequence and a number of charged amino acid Asp have been investigated, indicating that the presence of six additional Asp pronouncedly weakened the triple helical stability of peptide probe FAM-PCTP-D6 under physiological conditions (pH 7.4). FAM-PCTP-D6 could be directly applied without any pretreatment to recognize denatured collagen with high selectivity, whereas another dye-labeled peptide probe ROX-PCTP-D6 specifically targeted pathological collagen in various connective tissues of animal disease models and human patients. The inclusion of extra charged natural amino acids has been demonstrated as a convenient approach to create biocompatible collagen-targeting peptide probes with much weaker triple helical stability. Without the need for preheating treatment, these electrostatic repulsion-driven peptide probes provide a handy tool for histopathology staining, showing promising applications in collagen-involved diseases.
中文翻译：
静电排斥不稳定肽探针对病理性胶原蛋白的原位成像
强大的胶原蛋白检测的发展对于各种病理状况的诊断和治疗至关重要。由 (Gly-Pro-Hyp) n序列组成的肽探针因其卓越的胶原蛋白靶向能力而受到广泛关注，但不幸的是，它们的高三螺旋稳定性严重损害了这种能力。在此，我们报告了一种通过静电排斥降低 (Gly-Pro-Hyp) n序列的三螺旋倾向的有效策略。由 (Gly-Pro-Hyp) 7组成的一系列肽序列和一些带电氨基酸 Asp 已被研究，表明存在六个额外的 Asp 显着削弱了肽探针 FAM-PCTP-D6 在生理条件下 (pH 7.4) 的三螺旋稳定性。FAM-PCTP-D6无需任何预处理即可直接应用，以高选择性识别变性胶原蛋白，而另一种染料标记的肽探针ROX-PCTP-D6则专门针对动物疾病模型和人类患者的各种结缔组织中的病理性胶原蛋白。包含额外带电的天然氨基酸已被证明是一种方便的方法来创建具有弱得多的三螺旋稳定性的生物相容性胶原靶向肽探针。无需预热处理，
更新日期：2020-11-16
中文翻译：
静电排斥不稳定肽探针对病理性胶原蛋白的原位成像
强大的胶原蛋白检测的发展对于各种病理状况的诊断和治疗至关重要。由 (Gly-Pro-Hyp) n序列组成的肽探针因其卓越的胶原蛋白靶向能力而受到广泛关注，但不幸的是，它们的高三螺旋稳定性严重损害了这种能力。在此，我们报告了一种通过静电排斥降低 (Gly-Pro-Hyp) n序列的三螺旋倾向的有效策略。由 (Gly-Pro-Hyp) 7组成的一系列肽序列和一些带电氨基酸 Asp 已被研究，表明存在六个额外的 Asp 显着削弱了肽探针 FAM-PCTP-D6 在生理条件下 (pH 7.4) 的三螺旋稳定性。FAM-PCTP-D6无需任何预处理即可直接应用，以高选择性识别变性胶原蛋白，而另一种染料标记的肽探针ROX-PCTP-D6则专门针对动物疾病模型和人类患者的各种结缔组织中的病理性胶原蛋白。包含额外带电的天然氨基酸已被证明是一种方便的方法来创建具有弱得多的三螺旋稳定性的生物相容性胶原靶向肽探针。无需预热处理，
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