以分子動力模擬探討改質玻尿酸抑制基質金屬蛋白酶活性之分子機制

Abstract

Hyaluronan (HA) is a natural linear polysaccharide composed of disaccharide repeating units. HA is widely used in cosmetics and skin care product due to its excellent moisturizing ability. Recently, a novel derivative of hyaluronan, named Hya-HEAL+, has been synthesized and shown to have great ability in anti-aging skin care product applications. The novel derivative of hyaluronan (Hya-HEAL+) is modified with histidine side chain and hydrophobic group with a 30% to 50% degree of substitution of repeating units. Experimental results have shown that the novel derivative of hyaluronan (Hya-HEAL+) can effectively inhibit MMP-1, 3, 2, 9 (matrix metalloproteinase) which are enzymes that degrade collagen. By inhibiting the activity of MMP, the Hya-HEAL+ prevents the decomposition of collagen and shows an anti-aging effect. However, the molecular mechanisms of the inhabitation of MMP are still not clear. In this study, we investigate the molecular structure of Hya-HEAL+ and the molecular mechanisms of the inhibitory effect of Hya-HEAL+ on MMP through a full atomistic simulation approach. From nano-scale, we find that the hydrophobic group on Hya-HEAL+ is responsible for the structural difference between HA and Hya-HEAL+. Hya-HEAL+ interacts with MMP through hydrogen bonds, hydrophobic group and chelation of the active site zinc. The hydrophobic group increases the binding ability. Hya-HEAL+ binds to MMP and effectively prevents collagen degradation to achieve an anti-aging effect. This study provides fundamental insights into the conformations of Hya-HEAL+ and the binding pose of Hya-HEAL+ to MMP and help explaining the molecular properties and molecular mechanisms of the inhibitory effect of Hya-HEAL+ on MMP.