S-(pyridin-2-ylmethyl)-Fmoc-L-cysteine | 1411634-70-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: S-(pyridin-2-ylmethyl)-Fmoc-L-cysteine
• CAS: 1411634-70-2
• 化学式: C₂₄H₂₂N₂O₄S
• 分子量: 434.516
• InChiKey: AGBCFAMPRLHGKP-QFIPXVFZSA-N

物化性质

• 沸点：
  673.4±55.0 °C(predicted)
• 密度：
  1.328±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

反应信息

• 作为产物：
  描述：

  S-(pyridin-2-ylmethyl)-L-cysteine 、 氯甲酸-9-芴基甲酯 在 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 以82%的产率得到S-(pyridin-2-ylmethyl)-Fmoc-L-cysteine
  参考文献：
  名称：

  Novel, Cysteine-Modified Chelation Strategy for the Incorporation of [M^I(CO)₃]⁺ (M = Re, ^99mTc) in an α-MSH Peptide

  摘要：

  Engineering peptide-based targeting agents with residues for site-specific and stable complexation of radionuclides is a highly desirable strategy for producing diagnostic and therapeutic agents for cancer and other diseases. In this report, a model N-S-N-py ligand (3) and a cysteine-derived alpha-melanocyte stimulating hormone (alpha-MSH) peptide (6) were used as novel demonstrations of a widely applicable chelation strategy for incorporation of the [M-I(CO)(3)](+) (M = Re, Tc-99m) core into peptide-based molecules for radiopharmaceutical applications. The structural details of the core ligand metal complexes as model systems were demonstrated by full chemical characterization of fac-[Re-I(CO)(3)(N,S,N-py-3)](+) (4) and comparative high-performance liquid chromatography (HPLC) analysis between 4 and [Tc-99m(I)(CO)(3)(N,S,N-py-3)](+) (4a). The alpha-MSH analogue bearing the N-S-N-py chelate on a modified cysteine residue (6) was generated and complexed with [M-I(CO)(3)](+) to confirm the chelation strategy's utility when applied in a peptide-based targeting agent. Characterization of the Re-I(CO)(3)-6 peptide conjugate (7) confirmed the efficient incorporation of the metal center, and the Tc-99m(I)(CO)(3)-6 analogue (7a) was explored as a potential single photon emission computed tomography (SPECT) compound for imaging the melanocortin 1 receptor (MC1R) in melanoma. Peptide 7a showed excellent radiolabeling yields and in vitro stability during amino acid challenge and serum stability assays. In vitro B16F10 melanoma cell uptake of 7a reached a modest value of 2.3 +/- 0.08% of applied activity at 2 h at 37 degrees C, while this uptake was significantly reduced by coincubation with a nonlabeled a-MSH analogue, NAPamide (3.2 mu M) (P < 0.05). In vivo SPECT/X-ray computed tomography (SPECT/CT) imaging and biodistribution of 7a were evaluated in a B16F10 melanoma xenografted mouse model SPECT/CT imaging clearly visualized the tumor at 1 h post injection (p.i.) with high tumor-to-background contrast Blocking studies with coinjected NAPamide (10 mg per kg of mouse body weight) confirmed the in vivo specificity of 7a for MC1R-positive tumors. Biodistribution results with 7a yielded a moderate tumor uptake of 1.20 +/- 0.09 percentage of the injected radioactive dose per gram of tissue (%ID/g) at 1 h p.i. Relatively high uptake of 7a was also seen in the kidneys and liver at 1 h p.i. (6.55 +/- 0.36% ID/g and 444 +/- 0.17% ID/g, respectively), although reduced kidney uptake was seen at 4 h p.i. (3.20 +/- 0.48% ID/g). These results demonstrate the utility of the novel [M-I(CO)(3)](+) chelation strategy when applied in a targeting peptide.

  DOI：

  10.1021/bc300509k