Highly selective and pH responsive adsorption of ZIF-8 for angiotensin-converting enzyme (ACE) inhibitory active peptides and its mechanism

Abstract

Searching adsorbents for high recognition and adsorption capacities of active peptides has become the hotspot of scientific research in the screening and purification of peptides. In this work, we selected MOFs materials with good biocompatibility to systematically investigated for the selective adsorption of highly active ACE inhibitory peptides. Herein, five typical kinds of metal organic frameworks (MOFs) were initially screened for their adsorption capacities towards di-peptide (CW) having ultra-high angiotensin-converting enzyme (ACE) inhibitory activity (IC50 = 0.16 μM). The effects of their pore sizes and surface potentials on CW adsorption capacity were explored in this work. Among these MOFs, ZIF-8 was chosen as a di-peptide adsorbent due to its excellent adsorption capacity of CW (0.382 mmol/g). Besides, the adsorption behavior of ZIF-8 for di-peptides in the mixed solution was systematically explored. Experimental results indicated that ZIF-8 exhibited highly specific adsorption towards CW while showing very low and almost non-adsorption for the two inactive peptides, DD and RR. In their ternary peptide solution (molar ratio: CW/DD/RR = 1/10/10) for simulated protein hydrolysate, ZIF-8 displayed ultra-high adsorption selectivity (α = 46.6) for CW and thus enhanced almost 70.9 times the ACE inhibitory activity for the enriched solution. Meanwhile, molecular simulation revealed that ZIF-8 had high recognition towards CW, which was primarily attributed to synergistic mechanisms of electrostatic attraction, NH/SH···π interaction, and pore size screening of ZIF-8 towards CW. Interestingly, ZIF-8 was discovered for the first time to have a distinct pH-responsive property towards CW enrichment. Based on this property, pH-responsive adsorption was carried out with desorption over ZIF-8, and a stable regeneration process for 5 continuous adsorption/desorption cycles was accomplished. Collectively, this work proved that MOFs have promising application prospects in the field of peptide adsorption.