COUPLING DIFFICULTY ASSOCIATED WITH INTERCHAIN CLUSTERING AND PHASE-TRANSITION IN SOLID-PHASE PEPTIDE-SYNTHESIS
COUPLING DIFFICULTY ASSOCIATED WITH INTERCHAIN CLUSTERING AND PHASE-TRANSITION IN SOLID-PHASE PEPTIDE-SYNTHESIS
复制标题
DOI：
10.1021/ja00154a004
复制
发表时间：
1995-12-13
影响因子：
15
通讯作者：
LU, YA
中科院分区：
文献类型：
--
作者：
TAM, JP;LU, YA
我们开发了一个包含聚类肽链的模型来评估固相肽合成中与链间相互作用相关的耦合困难。我们的研究结果揭示了两个新发现。首先，在相似的肽基负载水平下，传统的分散肽链模型和我们的聚类肽链模型在溶剂化特性上存在显著差异。在完成8个残基的肽段时，当肽段含量为bbb61 %时，分散链模型的溶剂化体积比初始干燥树脂增加了20-30倍，在极性和非极性溶剂中都比聚集链模型的溶剂化体积高4-5倍。溶剂化的减少类似于树脂支架交联的效果，导致溶胀能力差。其次，当肽负载达到约50%的肽基树脂时，有一个聚苯乙烯到聚酰胺的过渡。在这一过渡阶段，肽基树脂在极性非质子溶剂和疏水溶剂中膨胀和生长均达到最低点。此外，相变也是非质子极性溶剂N，N-二甲基甲酰胺比非极性溶剂二氯甲烷具有更好的树脂溶胀性的交叉点。在非质子极性溶剂中，溶胀能力与偶联产率之间存在良好的相关性。非质子极性溶剂NMP与高温耦合相结合是提高耦合效率的最有效方法。因此，我们的研究结果提供了与链间相互作用相关的耦合困难的证据，链聚类和相变加剧了耦合困难。
We have developed a model containing clustered peptide chains to evaluate coupling difficulties associated with interchain interactions in solid phase peptide synthesis. Our results revealed two new findings. First, there was a significant difference in solvation properties between the conventional dispersed and our clustered peptide chain models at a similar level of peptidyl loading. At the completion of an eight-residue peptide, with a peptide content of >61%, the solvated volumes of a dispersed chain model increased 20-30-fold over the initial dry resin and were about 4-5-fold higher than those of the clustered chain model in both polar and nonpolar solvents. The decrease in solvation mimics the effect of higher cross-linking of resin supports, leading to poor swelling ability. Second, there was a polystyrene to polyamide transition when the peptide loading reached approximately 50% of the peptidyl resin. In this transition phase, the swelling and growth of the peptidyl resin reached the lowest point in both polar aprotic and hydrophobic solvents. Furthermore, the phase transition was also the crossover point where the aprotic polar solvent N,N-dimethylformamide provided better resin swellability than the nonpolar solvent dichloromethane. A good correlation between swelling ability and the coupling yield in aprotic polar solvents was also found. A combination of the aprotic polar solvent NMP and coupling at elevated temperature was found to be the most efficient to increase coupling efficiency. Thus, our results provide evidence for coupling difficulties associated with the interchain interactions exacerbated by chain clustering and phase transition.