Department of Experimental Diagnostic Imaging, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, United States.
J Med Chem. 2011 Mar 24;54(6):1825-35. doi: 10.1021/jm101477d. Epub 2011 Feb 24.
A 14-residue phosphatidylserine (PS)-binding peptide FNFRLKAGQKIRFG (PSBP-0) was scanned with Ala. In addition, a radiometal chelator (SAAC) was introduced at selected sites of the lead peptides. Substitution of the Gln(6) residue in PSBP-0 with Ala resulted in a significant increase in binding affinity to PS as determined by surface plasmon resonance sensorgrams. The binding affinity of the resulting peptide FNFRLKAGAKIRFG (PSBP-6, molecular mass = 1623 Da) to PS (K(d) ∼ 100 nM) increased 10-fold as compared to PSBP-0 (K(d) ∼ 1.38 μM). Introduction of SAAC-Re to the N terminus of PSBP-6 further increased the binding affinity of the resulting peptide SAAC(Re)-PSBP-6 (K(d) ∼ 26 nM). SAAC(Re)-PSBP-6 shows specific binding to apoptotic cells in cell-based assays. Biodistribution studies showed significantly higher uptake of SAAC((99 m)Tc)-PSBP-6 in B16/F10 melanoma treated with poly(L-glutamic acid)-paclitaxel than untreated tumors (4.06 ± 0.55% ID/g vs 1.61 ± 0.33% ID/g, P = 0.00011). SAAC((99 m)Tc)-PSBP-6 is a promising probe for noninvasive imaging of apoptotic cells.
一段由 14 个氨基酸组成的磷脂酰丝氨酸（PS）结合肽 FNFRLKAGQKIRFG（PSBP-0）被进行丙氨酸扫描。此外，在先导肽的选定部位引入了放射性金属螯合剂（SAAC）。PSBP-0 中 Gln（6）残基被丙氨酸取代，导致与 PS 的结合亲和力显著增加，这通过表面等离子体共振传感器图谱确定。所得肽 FNFRLKAGAKIRFG（PSBP-6，分子量=1623 Da）与 PS 的结合亲和力（Kd∼100 nM）与 PSBP-0（Kd∼1.38 μM）相比增加了 10 倍。将 SAAC-Re 引入 PSBP-6 的 N 端进一步增加了所得肽 SAAC（Re）-PSBP-6（Kd∼26 nM）的结合亲和力。SAAC（Re）-PSBP-6 在基于细胞的测定中显示出对凋亡细胞的特异性结合。生物分布研究表明，与未治疗的肿瘤相比，用聚（L-谷氨酸）-紫杉醇处理的 B16/F10 黑色素瘤中 SAAC（99mTc）-PSBP-6 的摄取显著更高（4.06±0.55% ID/g 比 1.61±0.33% ID/g，P=0.00011）。SAAC（99mTc）-PSBP-6 是一种很有前途的用于凋亡细胞非侵入性成像的探针。
