Rocchi S, Picard F, Vamecq J, Gelman L, Potier N, Zeyer D, Dubuquoy L, Bac P, Champy M F, Plunket K D, Leesnitzer L M, Blanchard S G, Desreumaux P, Moras D, Renaud J P, Auwerx J
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch, France.
Mol Cell. 2001 Oct;8(4):737-47. doi: 10.1016/s1097-2765(01)00353-7.
FMOC-L-Leucine (F-L-Leu) is a chemically distinct PPARgamma ligand. Two molecules of F-L-Leu bind to the ligand binding domain of a single PPARgamma molecule, making its mode of receptor interaction distinct from that of other nuclear receptor ligands. F-L-Leu induces a particular allosteric configuration of PPARgamma, resulting in differential cofactor recruitment and translating in distinct pharmacological properties. F-L-Leu activates PPARgamma with a lower potency, but a similar maximal efficacy, than rosiglitazone. The particular PPARgamma configuration induced by F-L-Leu leads to a modified pattern of target gene activation. F-L-Leu improves insulin sensitivity in normal, diet-induced glucose-intolerant, and in diabetic db/db mice, yet it has a lower adipogenic activity. These biological effects suggest that F-L-Leu is a selective PPARgamma modulator that activates some (insulin sensitization), but not all (adipogenesis), PPARgamma-signaling pathways.
芴甲氧羰基-L-亮氨酸（F-L-Leu）是一种化学性质独特的过氧化物酶体增殖物激活受体γ（PPARγ）配体。两分子的F-L-Leu与单个PPARγ分子的配体结合域结合，使其与其他核受体配体的受体相互作用模式不同。F-L-Leu诱导PPARγ形成特定的变构构象，导致不同的辅因子募集，并转化为不同的药理学特性。与罗格列酮相比，F-L-Leu激活PPARγ的效力较低，但最大功效相似。F-L-Leu诱导的特定PPARγ构象导致靶基因激活模式改变。F-L-Leu可改善正常、饮食诱导的葡萄糖不耐受以及糖尿病db/db小鼠的胰岛素敏感性，但其脂肪生成活性较低。这些生物学效应表明，F-L-Leu是一种选择性PPARγ调节剂，它激活一些（胰岛素增敏）而非全部（脂肪生成）PPARγ信号通路。
