Dual inhibitory pathways of metallofullerenol Gd@C₈₂(OH)₂₂ on matrix metalloproteinase-2: molecular insight into drug-like nanomedicine.

ABSTRACT: Cancer metastasis is an important criterion to evaluate tumor malignancy. Matrix metalloproteinases (MMPs) play a crucial role in cancer proliferation and migration by virtue of their proteolytic functions in angiogenesis and extracelluar matrix (ECM) degradation, making them potential targets of anti-metastaic therapeutics. Recently we showed with both in vivo and in vitro experiments that metallofullerenol Gd@C82(OH)22 can effectively inhibit MMP-2 and MMP-9 with high antitumoral efficacy. Furthermore, our in silico study revealed that Gd@C82(OH)22 could indirectly inhibit the proteolysis of MMP-9 via allosteric modulation exclusively at the ligand specificity S1' loop. Here, we expand our study toward another gelatinase, MMP-2, using molecular dynamics simulations. Despite the high stru

SUBMITTER: Kang SG 

PROVIDER: S-EPMC3998016 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature