TREN (tris(2-aminoethyl)amine): An effective scaffold for the assembly of triple helical collagen mimetic structures

TREN (tris(2-aminoethyl)amine): An effective scaffold for the assembly of triple helical collagen mimetic structures
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DOI:
10.1021/ja0209621
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发表时间:
2002-11-27
影响因子:
15
通讯作者:
Goodman, M
Goodman, M
中科院分区:
化学1区
文献类型:
--
作者:
Kwak, J;De Capua, A;Goodman, M

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一种新的支架,Tren-(suc-OH)(3),其中Tren是三(2-氨基乙基)胺,suc是琥珀酸间隔基,组装了由Gly-Nleu-Pro序列(Nleu表示N-异丁基甘氨酸)组成的三螺旋。广泛的生物物理研究表明,Tren-[suc-(Gly-Nleu-Pro)(N)-NH2](3)(n=5和6)在溶液中形成稳定的三螺旋结构。对Tren组装和Kta组装的胶原蛋白模拟物(Kta表示Kemp三酸,1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic酸)的比较分析表明,Tren支架的柔性在诱导三螺旋结构方面优于Kta支架。这种效果很可能源于Tren支架的灵活性,它允许三个肽链调整它们的寄存器,以实现更紧密的三重螺旋堆积。
A new scaffold, TREN-(suc-OH)(3) where TREN is tris(2-aminoethyl)amine and suc is the succinic acid spacers, was incorporated to assemble triple helices composed of Gly-Nleu-Pro sequences (Nleu denotes N-isobutylglycine). Extensive biophysical studies which include denaturation studies, CD and NMR spectroscopy, and molecular modeling demonstrated that TREN-[suc-(Gly-Nleu-PrO)(n)-NH2](3) (n = 5 and 6) form stable triple helical structures in solution. A comparative analysis of TREN-assembled and KTA-assembled Collagen mimetics (KTA denotes Kemp triacid, 1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid) indicates that the flexibility of the TREN scaffold is superior to the KTA scaffold in inducing triple helicity. This effect most likely arises from the flexibility of the TREN scaffold which allows the three peptide chains to adjust their register for a tighter triple helical packing.