| 1255763-76-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• CAS: 1255763-76-8
• 化学式: C₅₄H₇₂N₁₆O₇
• 分子量: 1057.27
• InChiKey: PBRHFDSJFAYGCD-FQEQRRFLSA-N

反应信息

• 作为产物：
  描述：

  在 sodium azide 作用下， 以 二甲基亚砜 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Synthesis, Characterization, and Thermodynamic Study of a Polyvalent Lytic Peptide−Polymer Conjugate As Novel Anticancer Agent

  摘要：

  We designed and synthesized a new polyvalent lytic peptide-polymer conjugate as a novel chemotherapeutic agent capable of overcoming multidrug resistance. A hexapeptide (KWKWKW or (KW)(3)) was designed and conjugated to dextran in multiple copies to afford a polyvalent conjugate. A robust synthesis procedure involving click chemistry and the detailed characterization of the conjugate were reported here. The conjugate Dex-(KW)(3) exhibited significantly enhanced anticancer potency in vitro by up to 500-fold compared to monomeric (KW)(3). The LC50 value was comparable to that of conventional lytic peptides which have more than 20 residues. No hemolytic activity was shown by the conjugates up to 300 mu M. Thermodynamic study indicated that the binding of conjugates was predominantly entropy-driven while the binding of free peptides was mainly enthalpy-driven, implying a deeper penetration of conjugate into the core of lipid bilayer. The binding affinity of conjugate to neutral membrane is much higher than that to free peptide (K-conj approximate to 8822.9 M-1, K-pep approximate to 1884.7 M-1). In binding to negatively charged membrane, the conjugate surpassed free peptides at high concentrations when the binding of free peptides became saturated. The higher binding capability, attributed to the high local concentration of peptides mounted on a polymer backbone, explains the superior anticancer activity of polyvalent Dex-(KW)(3).

  DOI：

  10.1021/bc1002899