| 941290-95-5

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• CAS: 941290-95-5
• 化学式: C₁₀₆H₁₅₆N₃₄O₂₂
• 分子量: 2258.62
• InChiKey: XDCSEJHJZMUVNG-CFLDLIDLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.55
• 重原子数：
  162.0
• 可旋转键数：
  66.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  903.2
• 氢给体数：
  31.0
• 氢受体数：
  30.0

反应信息

• 作为反应物：
  描述：

  4-(N-马来酰亚胺基甲基)环己烷-1-羧酸琥珀酰亚胺酯 、 以 aq. phosphate buffer 为溶剂， 生成
  参考文献：
  名称：

  Preparation and Characterization of Albumin Conjugates of a Truncated Peptide YY Analogue for Half-Life Extension

  摘要：

  Recombinant human serum albumin (HSA) conjugates of a 15-amino-acid truncated peptide YY (PYY) analogue were prepared using three heterobifunctional linkers [succinimidyl 4-[N-maleimidomethyl]cyclohexane-1-carboxylate (SMCC), 6-maleimidohexanoic acid N-hydroxysuccinimide ester (MHS), and N-[gamma-maleimidobutyryloxy]sulfosuccinimide ester (GMBS)] in 2 synthetic steps involving (I) reaction of succinimidyl ester on linker with epsilon-amine of Lys2 on the peptide and (2) reaction of maleimide on peptide linker with free thiol of Cysteine 34 (Cys34) on albumin. In-process controls using ESI LC-MS were used to follow reactions and identify reaction products. Proteolytic digests of the conjugate revealed that peptide conjugation occurs at Cys34 on HSA. Conjugates were assayed in cell-based assays to determine potency at the human Y2-receptor, and selectivity at the human Y1-, Y4-, and Y5-receptors using a calcium flux assay. All three conjugates assayed were selective agonists of the Y2-receptor, and displayed nanomolar potencies. MCC and MH conjugates were selected for acute PK/PD studies in DIO mice. Significant reduction in food intake was observed with the MH conjugate, which lasted for 24 h at the 10 mg (or 4 mu mol)/kg dose. While the MCC conjugate exhibited greater potency in vitro, it was slightly less effective than the MH conjugate in vivo with respect to reduction in food intake. Both conjugates were significantly less active than the peptide coupled to a 30 kDa PEG. The observed T-1/2 (8-9 h) for both conjugates was significantly lower than that observed for the PEGylated peptide (similar to 25 h). These results suggest that, as compared with the unmodified and PEGylated peptide, the extended circulation half-life of albumin conjugates is mediated through uptake and recirculation by FcRn, and allometric scaling methods are necessary to account for interspecies variation in pharmacokinetic properties.

  DOI：

  10.1021/bc400340z