Objective

To elucidate the structure–activity relationships (SARs) of proanthocyanidins (PACs) with type I collagen using sixteen chemically defined PACs with degree of polymerization (DP) 2–6.

Methods

Under a dentin model, the biomimicry of PACs with type I collagen was investigated by dynamic mechanical analysis (DMA) and infrared spectroscopy. The dentin matrix was modified with PACs from Pinus massoniana [monomers (Mon-1 and Mon-2), dimers (Dim-1-Dim-4), trimers (Tri-1-Tri-4), tetramers (Tet-1-Tet-5), and hexamer (Hex-1)]. A strain sweep method in a 3-point bending submersion clamp was used to assess the viscoelastic properties [storage (E’), loss (E”), and complex moduli (E*) and tan δ] of the dentin matrix before and after biomodification. Biochemical analysis of the dentin matrix was assessed with FTIR spectroscopy. Data were statistically analyzed using one-way ANOVA and post-hoc tests (α = 0.05).

Results

DP had a significant effect on modified dentin moduli (tetramers ≈ trimers > hexamers ≈ dimers > monomers ≈ control, p < 0.001). Trimers and tetramers yielded 6- to 8-fold increase in the mechanical properties of modified dentin and induced conformational changes to the secondary structure of collagen. Modifications to the tertiary structure of collagen was shown in all PAC modified-dentin matrices.

Significance

Findings establish three key SARs: (i) increasing DP generally enhances biomimicry potential of PACs in modulating the mechanical and chemical properties of dentin (ii) the secondary structure of dentin collagen is affected by the position of B-type inter-flavanyl linkages (4β → 6 and 4β → 8); and (iii) the terminal monomeric flavan-3-ol unit plays a modulatory role in the viscoelasticity of dentin.

中文翻译：

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揭示原花青素与牙本质胶原蛋白的构效关系

客观的

使用十六种化学定义的聚合度 (DP) 2-6 的 PAC 阐明原花青素 (PAC) 与 I 型胶原蛋白的构效关系 (SAR)。

方法

在牙本质模型下，通过动态力学分析（DMA）和红外光谱研究了具有 I 型胶原蛋白的 PAC 的仿生学。牙本质基质用来自马尾松的 PAC [单体 (Mon-1 和 Mon-2)、二聚体 (Dim-1-Dim-4)、三聚体 (Tri-1-Tri-4)、四聚体 (Tet-1- Tet-5) 和六聚体 (Hex-1)]。使用 3 点弯曲浸没夹具中的应变扫描方法来评估牙本质基质前后的粘弹性 [存储 (E')、损耗 (E”) 和复模量 (E*) 和 tan δ]生物修饰。牙本质基质的生化分析采用 FTIR 光谱法进行评估。使用单因素方差分析和事后检验对数据进行统计分析（α = 0.05）。

结果

DP 对改性牙本质模量有显着影响（四聚体 ≈ 三聚体 > 六聚体 ≈ 二聚体 > 单体 ≈ 对照，p < 0.001）。三聚体和四聚体使改性牙本质的机械性能提高 6 到 8 倍，并诱导胶原二级结构的构象变化。在所有 PAC 修饰的牙本质基质中都显示了对胶原三级结构的修饰。

意义

研究结果确定了三个关键的 SAR：（i）增加 DP 通常会增强 PAC 在调节牙本质的机械和化学性质方面的仿生潜力（​​ii）牙本质胶原蛋白的二级结构受 B 型黄烷间键位置的影响（4 β → 6 和 4 β → 8)；(iii) 末端单体黄烷-3-醇单元在牙本质的粘弹性中起调节作用。